158 results on '"James P. McAllister"'
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2. Outcomes of the 2019 hydrocephalus association workshop, 'Driving common pathways: extending insights from posthemorrhagic hydrocephalus'
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Jason K. Karimy, Jessie C. Newville, Cameron Sadegh, Jill A. Morris, Edwin S. Monuki, David D. Limbrick, James P. McAllister II, Jenna E. Koschnitzky, Maria K. Lehtinen, and Lauren L. Jantzie
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Hydrocephalus ,Posthemorrhagic ,Post-infectious ,Intraventricular hemorrhage ,Germinal matrix hemorrhage ,Cilia ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract The Hydrocephalus Association (HA) workshop, Driving Common Pathways: Extending Insights from Posthemorrhagic Hydrocephalus, was held on November 4 and 5, 2019 at Washington University in St. Louis. The workshop brought together a diverse group of basic, translational, and clinical scientists conducting research on multiple hydrocephalus etiologies with select outside researchers. The main goals of the workshop were to explore areas of potential overlap between hydrocephalus etiologies and identify drug targets that could positively impact various forms of hydrocephalus. This report details the major themes of the workshop and the research presented on three cell types that are targets for new hydrocephalus interventions: choroid plexus epithelial cells, ventricular ependymal cells, and immune cells (macrophages and microglia).
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- 2023
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3. The effect of A1 and A2 reactive astrocyte expression on hydrocephalus shunt failure
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Fatemeh Khodadadei, Rooshan Arshad, Diego M. Morales, Jacob Gluski, Neena I. Marupudi, James P. McAllister, David D. Limbrick, and Carolyn A. Harris
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Neuroprosthetic device failure ,Hydrocephalus ,Glial Scar ,A1 and A2 reactive astrocyte phenotype ,Targeted drug delivery ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background The composition of tissue obstructing neuroprosthetic devices is largely composed of inflammatory cells with a significant astrocyte component. In a first-of-its-kind study, we profile the astrocyte phenotypes present on hydrocephalus shunts. Methods qPCR and RNA in-situ hybridization were used to quantify pro-inflammatory (A1) and anti-inflammatory (A2) reactive astrocyte phenotypes by analyzing C3 and EMP1 genes, respectively. Additionally, CSF cytokine levels were quantified using ELISA. In an in vitro model of astrocyte growth on shunts, different cytokines were used to prevent the activation of resting astrocytes into the A1 and A2 phenotypes. Obstructed and non-obstructed shunts were characterized based on the degree of actual tissue blockage on the shunt surface instead of clinical diagnosis. Results The results showed a heterogeneous population of A1 and A2 reactive astrocytes on the shunts with obstructed shunts having a significantly higher proportion of A2 astrocytes compared to non-obstructed shunts. In addition, the pro-A2 cytokine IL-6 inducing proliferation of astrocytes was found at higher concentrations among CSF from obstructed samples. Consequently, in the in vitro model of astrocyte growth on shunts, cytokine neutralizing antibodies were used to prevent activation of resting astrocytes into the A1 and A2 phenotypes which resulted in a significant reduction in both A1 and A2 growth. Conclusions Therefore, targeting cytokines involved with astrocyte A1 and A2 activation is a promising intervention aimed to prevent shunt obstruction.
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- 2022
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4. Acquired hydrocephalus is associated with neuroinflammation, progenitor loss, and cellular changes in the subventricular zone and periventricular white matter
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Maria Garcia-Bonilla, Leandro Castaneyra-Ruiz, Sarah Zwick, Michael Talcott, Ayodamola Otun, Albert M. Isaacs, Diego M. Morales, David D. Limbrick, and James P. McAllister
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Kaolin-induced hydrocephalus ,Pig model ,Ventriculomegaly ,Subventricular zone reduction ,White matter alteration ,Neuroinflammation ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Hydrocephalus is a neurological disease with an incidence of 80–125 per 100,000 births in the United States. Neuropathology comprises ventriculomegaly, periventricular white matter (PVWM) alterations, inflammation, and gliosis. We hypothesized that hydrocephalus in a pig model is associated with subventricular and PVWM cellular alterations and neuroinflammation that could mimic the neuropathology described in hydrocephalic infants. Methods Hydrocephalus was induced by intracisternal kaolin injections in 35-day old female pigs (n = 7 for tissue analysis, n = 10 for CSF analysis). Age-matched sham controls received saline injections (n = 6). After 19–40 days, MRI scanning was performed to measure the ventricular volume. Stem cell proliferation was studied in the Subventricular Zone (SVZ), and cell death and oligodendrocytes were examined in the PVWM. The neuroinflammatory reaction was studied by quantifying astrocytes and microglial cells in the PVWM, and inflammatory cytokines in the CSF. Results The expansion of the ventricles was especially pronounced in the body of the lateral ventricle, where ependymal disruption occurred. PVWM showed a 44% increase in cell death and a 67% reduction of oligodendrocytes. In the SVZ, the number of proliferative cells and oligodendrocyte decreased by 75% and 57% respectively. The decrease of the SVZ area correlated significantly with ventricular volume increase. Neuroinflammation occurred in the hydrocephalic pigs with a significant increase of astrocytes and microglia in the PVWM, and high levels of inflammatory interleukins IL-6 and IL-8 in the CSF. Conclusion The induction of acquired hydrocephalus produced alterations in the PVWM, reduced cell proliferation in the SVZ, and neuroinflammation.
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- 2022
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5. Biochemical profile of human infant cerebrospinal fluid in intraventricular hemorrhage and post-hemorrhagic hydrocephalus of prematurity
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Ayodamola Otun, Diego M. Morales, Maria Garcia-Bonilla, Seth Goldberg, Leandro Castaneyra-Ruiz, Yan Yan, Albert M. Isaacs, Jennifer M. Strahle, James P. McAllister, and David D. Limbrick
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Post-hemorrhagic hydrocephalus (PHH) ,Intraventricular hemorrhage (IVH) ,CSF osmolality ,CSF electrolytes ,Cerebrospinal fluid (CSF) ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHH) have a complex pathophysiology involving inflammatory response, ventricular zone and cell–cell junction disruption, and choroid-plexus (ChP) hypersecretion. Increased cerebrospinal fluid (CSF) cytokines, extracellular matrix proteins, and blood metabolites have been noted in IVH/PHH, but osmolality and electrolyte disturbances have not been evaluated in human infants with these conditions. We hypothesized that CSF total protein, osmolality, electrolytes, and immune cells increase in PHH. Methods CSF samples were obtained from lumbar punctures of control infants and infants with IVH prior to the development of PHH and any neurosurgical intervention. Osmolality, total protein, and electrolytes were measured in 52 infants (18 controls, 10 low grade (LG) IVH, 13 high grade (HG) IVH, and 11 PHH). Serum electrolyte concentrations, and CSF and serum cell counts within 1-day of clinical sampling were obtained from clinical charts. Frontal occipital horn ratio (FOR) was measured for estimating the degree of ventriculomegaly. Dunn or Tukey’s post-test ANOVA analysis were used for pair-wise comparisons. Results CSF osmolality, sodium, potassium, and chloride were elevated in PHH compared to control (p = 0.012 −
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- 2021
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6. A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments
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James P. McAllister, Michael R. Talcott, Albert M. Isaacs, Sarah H. Zwick, Maria Garcia-Bonilla, Leandro Castaneyra-Ruiz, Alexis L. Hartman, Ryan N. Dilger, Stephen A. Fleming, Rebecca K. Golden, Diego M. Morales, Carolyn A. Harris, and David D. Limbrick
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Hydrocephalus ,Animal models ,Kaolin ,Acquired hydrocephalus ,Shunt ,Ventriculomegaly ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Many animal models have been used to study the pathophysiology of hydrocephalus; most of these have been rodent models whose lissencephalic cerebral cortex may not respond to ventriculomegaly in the same way as gyrencephalic species and whose size is not amenable to evaluation of clinically relevant neurosurgical treatments. Fewer models of hydrocephalus in gyrencephalic species have been used; thus, we have expanded upon a porcine model of hydrocephalus in juvenile pigs and used it to explore surgical treatment methods. Methods Acquired hydrocephalus was induced in 33–41-day old pigs by percutaneous intracisternal injections of kaolin (n = 17). Controls consisted of sham saline-injected (n = 6) and intact (n = 4) animals. Magnetic resonance imaging (MRI) was employed to evaluate ventriculomegaly at 11–42 days post-kaolin and to plan the surgical implantation of ventriculoperitoneal shunts at 14–38-days post-kaolin. Behavioral and neurological status were assessed. Results Bilateral ventriculomegaly occurred post-induction in all regions of the cerebral ventricles, with prominent CSF flow voids in the third ventricle, foramina of Monro, and cerebral aqueduct. Kaolin deposits formed a solid cast in the basal cisterns but the cisterna magna was patent. In 17 untreated hydrocephalic animals. Mean total ventricular volume was 8898 ± 5917 SD mm3 at 11–43 days of age, which was significantly larger than the baseline values of 2251 ± 194 SD mm3 for 6 sham controls aged 45–55 days, (p
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- 2021
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7. A multicenter retrospective study of heterogeneous tissue aggregates obstructing ventricular catheters explanted from patients with hydrocephalus
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Prashant Hariharan, Jeffrey Sondheimer, Alexandra Petroj, Jacob Gluski, Andrew Jea, William E. Whitehead, Sandeep Sood, Steven D. Ham, Brandon G. Rocque, Neena I. Marupudi, James P. McAllister, David Limbrick, Marc R. Del Bigio, and Carolyn A. Harris
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Hydrocephalus ,Biobank ,Ventriculoperitoneal shunt ,Shunt failure ,Shunt obstruction ,Retrospective cohort ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Implantation of ventricular catheters (VCs) to drain cerebrospinal fluid (CSF) is a standard approach to treat hydrocephalus. VCs fail frequently due to tissue obstructing the lumen via the drainage holes. Mechanisms driving obstruction are poorly understood. This study aimed to characterize the histological features of VC obstructions and identify links to clinical factors. Methods 343 VCs with relevant clinical data were collected from five centers. Each hole on the VCs was classified by degree of tissue obstruction after macroscopic analysis. A subgroup of 54 samples was analyzed using immunofluorescent labelling, histology and immunohistochemistry. Results 61.5% of the 343 VCs analyzed had tissue aggregates occluding at least one hole (n = 211) however the vast majority of the holes (70%) showed no tissue aggregates. Mean age at which patients with occluded VCs had their first surgeries (3.25 yrs) was lower than in patients with non-occluded VCs (5.29 yrs, p
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- 2021
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8. Generation of Periventricular Reactive Astrocytes Overexpressing Aquaporin 4 Is Stimulated by Mesenchymal Stem Cell Therapy
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María García-Bonilla, Betsaida Ojeda-Pérez, Kirill Shumilov, Luis-Manuel Rodríguez-Pérez, Dolores Domínguez-Pinos, Javier Vitorica, Sebastián Jiménez, Reposo Ramírez-Lorca, Miriam Echevarría, Casimiro Cárdenas-García, Teresa Iglesias, Antonia Gutiérrez, James P. McAllister, David D. Limbrick, Patricia Páez-González, and Antonio J. Jiménez
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hydrocephalus ,aquaporin 4 ,astrocyte reaction ,mesenchymal stem cell ,stem cell therapy ,proteomic ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh mice, and the periventricular reaction was detected two weeks later. A protein expression analysis of the cerebral tissue differentiated the BM-MSC-treated mice from the controls and revealed effects on neural development. In in vivo and in vitro experiments, BM-MSCs stimulated the generation of periventricular reactive astrocytes overexpressing AQP4 and its regulatory protein kinase D-interacting substrate of 220 kDa (Kidins220). In the cerebral tissue, mRNA overexpression of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF1α), and transforming growth factor beta 1 (TGFβ1) could be related to the regulation of the astrocyte reaction and AQP4 expression. In conclusion, BM-MSC treatment in hydrocephalus can stimulate a key developmental process such as the periventricular astrocyte reaction, where AQP4 overexpression could be implicated in tissue recovery.
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- 2023
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9. Cerebrospinal fluid biomarkers of neuroinflammation in children with hydrocephalus and shunt malfunction
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Carolyn A. Harris, Diego M. Morales, Rooshan Arshad, James P. McAllister, and David D. Limbrick
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Neuroinflammation ,Cytokines ,Mmps ,Hydrocephalus ,Revisions ,Multiplex ELISA ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Approximately 30% of cerebrospinal fluid (CSF) shunt systems for hydrocephalus fail within the first year and 98% of all patients will have shunt failure in their lifetime. Obstruction remains the most common reason for shunt failure. Previous evidence suggests elevated pro-inflammatory cytokines in CSF are associated with worsening clinical outcomes in neuroinflammatory diseases. The aim of this study was to determine whether cytokines and matrix metalloproteinases (MMPs) contribute towards shunt failure in hydrocephalus. Methods Using multiplex ELISA, this study examined shunt failure through the CSF protein concentration profiles of select pro-inflammatory and anti-inflammatory cytokines, as well as select MMPs. Interdependencies such as the past number of previous revisions, length of time implanted, patient age, and obstruction or non-obstruction revision were examined. The pro-inflammatory cytokines were IL-1β, IL-2, IL-5, IL-6, IL-8, IL-12, IL-17, TNF-α, GM-CSF, IFN-γ. The anti-inflammatory cytokines were IL-4 and IL-10, and the MMPs were MMP-2, MMP-3, MMP-7, MMP-9. Protein concentration is reported as pg/mL for each analyte. Results Patient CSF was obtained at the time of shunt revision operation; all pediatric (
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- 2021
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10. Preterm intraventricular hemorrhage in vitro: modeling the cytopathology of the ventricular zone
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Leandro Castaneyra-Ruiz, James P. McAllister, Diego M. Morales, Steven L. Brody, Albert M. Isaacs, and David D. Limbrick
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Cell culture ,Neural stem cells ,Ependyma ,Ventricular zone ,Intraventricular hemorrhage ,Post- hemorrhagic hydrocephalus ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Severe intraventricular hemorrhage (IVH) is one of the most devastating neurological complications in preterm infants, with the majority suffering long-term neurological morbidity and up to 50% developing post-hemorrhagic hydrocephalus (PHH). Despite the importance of this disease, its cytopathological mechanisms are not well known. An in vitro model of IVH is required to investigate the effects of blood and its components on the developing ventricular zone (VZ) and its stem cell niche. To address this need, we developed a protocol from our accepted in vitro model to mimic the cytopathological conditions of IVH in the preterm infant. Methods Maturing neuroepithelial cells from the VZ were harvested from the entire lateral ventricles of wild type C57BL/6 mice at 1–4 days of age and expanded in proliferation media for 3–5 days. At confluence, cells were re-plated onto 24-well plates in differentiation media to generate ependymal cells (EC). At approximately 3–5 days, which corresponded to the onset of EC differentiation based on the appearance of multiciliated cells, phosphate-buffered saline for controls or syngeneic whole blood for IVH was added to the EC surface. The cells were examined for the expression of EC markers of differentiation and maturation to qualitatively and quantitatively assess the effect of blood exposure on VZ transition from neuroepithelial cells to EC. Discussion This protocol will allow investigators to test cytopathological mechanisms contributing to the pathology of IVH with high temporal resolution and query the impact of injury to the maturation of the VZ. This technique recapitulates features of normal maturation of the VZ in vitro, offering the capacity to investigate the developmental features of VZ biogenesis.
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- 2020
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11. Characterization of a multicenter pediatric-hydrocephalus shunt biobank
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Jacob Gluski, Paul Zajciw, Prashant Hariharan, Amanda Morgan, Diego M. Morales, Andrew Jea, William Whitehead, Neena Marupudi, Steven Ham, Sandeep Sood, James P. McAllister, David D. Limbrick, and Carolyn A. Harris
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Hydrocephalus ,Biobank ,Shunt failure ,Shunt obstruction ,CSF = cerebrospinal fluid ,Ventriculoperitoneal shunt ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Pediatric hydrocephalus is a devastating and costly disease. The mainstay of treatment is still surgical shunting of cerebrospinal fluid (CSF). These shunts fail at a high rate and impose a significant burden on patients, their families and society. The relationship between clinical decision making and shunt failure is poorly understood and multifaceted, but catheter occlusion remains the most frequent cause of shunt complications. In order to investigate factors that affect shunt failure, we have established the Wayne State University (WSU) shunt biobank. Methods To date, four hospital centers have contributed various components of failed shunts and CSF from patients diagnosed with hydrocephalus before adulthood. The hardware samples are transported in paraformaldehyde and transferred to phosphate-buffered saline with sodium azide upon deposit into the biobank. Once in the bank, they are then available for study. Informed consent is obtained by the local center before corresponding clinical data are entered into a REDCap database. Data such as hydrocephalus etiology and details of shunt revision history. All data are entered under a coded identifier. Results 293 shunt samples were collected from 228 pediatric patients starting from May 2015 to September 2019. We saw a significant difference in the number of revisions per patient between centers (Kruskal–Wallis H test, p value
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- 2020
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12. Opportunities in posthemorrhagic hydrocephalus research: outcomes of the Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop
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Jenna E. Koschnitzky, Richard F. Keep, David D. Limbrick, James P. McAllister, Jill A. Morris, Jennifer Strahle, and Yun C. Yung
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Hydrocephalus ,Posthemorrhagic ,Intraventricular hemorrhage ,Germinal matrix hemorrhage ,Blood brain barrier ,Premature ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract The Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop was held on July 25 and 26, 2016 at the National Institutes of Health. The workshop brought together a diverse group of researchers including pediatric neurosurgeons, neurologists, and neuropsychologists with scientists in the fields of brain injury and development, cerebrospinal and interstitial fluid dynamics, and the blood–brain and blood–CSF barriers. The goals of the workshop were to identify areas of opportunity in posthemorrhagic hydrocephalus research and encourage scientific collaboration across a diverse set of fields. This report details the major themes discussed during the workshop and research opportunities identified for posthemorrhagic hydrocephalus. The primary areas include (1) preventing intraventricular hemorrhage, (2) stopping primary and secondary brain damage, (3) preventing hydrocephalus, (4) repairing brain damage, and (5) improving neurodevelopment outcomes in posthemorrhagic hydrocephalus.
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- 2018
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13. Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus
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Gakwaya Habiyaremye, Diego M. Morales, Clinton D. Morgan, James P. McAllister, Travis S. CreveCoeur, Rowland H. Han, Mohamed Gabir, Brandon Baksh, Deanna Mercer, and David D. Limbrick
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Cytokines ,Chemokines ,Post-hemorrhagic ,Hydrocephalus ,CSF ,Cerebrospinal fluid ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Neuroinflammation has been implicated in the pathophysiology of post-hemorrhagic hydrocephalus (PHH) of prematurity, but no comprehensive analysis of signaling molecules has been performed using human cerebrospinal fluid (CSF). Methods Lumbar CSF levels of key cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF-β1, IFN-γ) and chemokines (XCL-1, CCL-2, CCL-3, CCL-19, CXCL-10, CXCL-11, CXCL-12) were measured using conventional and multiplexed Enzyme-linked Immunosorbent Assays and compared between preterm infants with PHH and those with no known neurological injury. The relationships between individual biomarker levels and specific CSF cell counts were examined. Results Total protein (TP) CSF levels were elevated in the PHH subjects compared to controls. CSF levels of IL-1α, IL-4, IL-6, IL-12, TNF-α, CCL-3, CCL-19, and CXCL-10 were significantly increased in PHH whereas XCL-1 was significantly decreased in PHH. When normalizing by TP, IL-1α, IL-1β, IL-10, IL-12, CCL-3, and CCL-19 levels were significantly elevated compared to controls, while XCL-1 levels remained significantly decreased. Among those with significantly different levels in both absolute and normalized levels, only absolute CCL-19 levels showed a significant correlation with CSF nucleated cells, neutrophils, and lymphocytes. IL-1β and CXCL-10 also were correlated with total cell count, nucleated cells, red blood cells, and neutrophils. Conclusions Neuroinflammation is likely to be an important process in the pathophysiology of PHH. To our knowledge, this is the first study to investigate CSF levels of chemokines in PHH as well as the only one to show XCL-1 selectively decreased in a diseased state. Additionally, CCL-19 was the only analyte studied that showed significant differences between groups and had significant correlation with cell count analysis. The selectivity of CCL-19 and XCL-1 should be further investigated. Future studies will further delineate the role of these cytokines and chemokines in PHH.
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- 2017
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14. Impaired neurogenesis with reactive astrocytosis in the hippocampus in a porcine model of acquired hydrocephalus
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Maria Garcia-Bonilla, Arjun Nair, Jason Moore, Leandro Castaneyra-Ruiz, Sarah H. Zwick, Ryan N. Dilger, Stephen A. Fleming, Rebecca K. Golden, Michael R. Talcott, Albert M. Isaacs, David D. Limbrick, and James P. McAllister
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Developmental Neuroscience ,Neurology - Published
- 2023
15. Characterization of a multicenter pediatric-hydrocephalus shunt biobank
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Andrew Jea, William E. Whitehead, Sandeep Sood, Prashant Hariharan, Neena Marupudi, Amanda Morgan, Paul Zajciw, Diego M. Morales, Carolyn A. Harris, Jacob Gluski, David D. Limbrick, Steven D. Ham, and James P. McAllister
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Male ,Pediatrics ,Disease ,lcsh:RC346-429 ,0302 clinical medicine ,Cerebrospinal fluid ,Informed consent ,Multicenter Studies as Topic ,Child ,Multicenter ,Biological Specimen Banks ,Cerebrospinal Fluid ,Translational ,General Medicine ,Cerebrospinal Fluid Shunts ,Ventriculoperitoneal shunt ,Exact test ,Neurology ,Child, Preschool ,030220 oncology & carcinogenesis ,Equipment Failure ,Female ,Shunt (electrical) ,Hydrocephalus ,Adult ,Reoperation ,medicine.medical_specialty ,Adolescent ,Young Adult ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,medicine ,Humans ,lcsh:Neurology. Diseases of the nervous system ,Retrospective Studies ,Biobank ,Improving surgical outcomes ,business.industry ,Research ,Infant ,Retrospective cohort study ,Retrospective cohort ,medicine.disease ,Shunt obstruction ,Etiology ,Shunt failure ,business ,CSF = cerebrospinal fluid ,030217 neurology & neurosurgery - Abstract
Background Pediatric hydrocephalus is a devastating and costly disease. The mainstay of treatment is still surgical shunting of cerebrospinal fluid (CSF). These shunts fail at a high rate and impose a significant burden on patients, their families and society. The relationship between clinical decision making and shunt failure is poorly understood and multifaceted, but catheter occlusion remains the most frequent cause of shunt complications. In order to investigate factors that affect shunt failure, we have established the Wayne State University (WSU) shunt biobank. Methods To date, four hospital centers have contributed various components of failed shunts and CSF from patients diagnosed with hydrocephalus before adulthood. The hardware samples are transported in paraformaldehyde and transferred to phosphate-buffered saline with sodium azide upon deposit into the biobank. Once in the bank, they are then available for study. Informed consent is obtained by the local center before corresponding clinical data are entered into a REDCap database. Data such as hydrocephalus etiology and details of shunt revision history. All data are entered under a coded identifier. Results 293 shunt samples were collected from 228 pediatric patients starting from May 2015 to September 2019. We saw a significant difference in the number of revisions per patient between centers (Kruskal–Wallis H test, p value Conclusion The retrospective analysis identified that differences exist between currently enrolled centers, although further work is needed before clinically actionable recommendations can be made. Moreover, the variables collected from this chart review explain a meaningful amount of variance in the number of revision surgeries. Future work will expand on the contribution of different site-specific and patient-specific factors to identify potential cause and effect relationships.
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- 2020
16. Microstructural Periventricular White Matter Injury in Post-hemorrhagic Ventricular Dilatation
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Dimitrios Alexopoulous, Sonika Dahiya, Jennifer Strahle, Leandro Castañeyra-Ruiz, Haley E. Botteron, Harri Merisaari, Sheng-Kwei Song, Jeffrey J. Neil, Joshua S. Shimony, Christopher D. Smyser, Sun Peng, Diego M. Morales, David D. Limbrick, Yan Yan, Ajit George, James P. McAllister, and Albert M. Isaacs
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Pathology ,medicine.medical_specialty ,business.industry ,Context (language use) ,Corpus callosum ,medicine.disease ,Hydrocephalus ,White matter ,Myelin ,medicine.anatomical_structure ,Intraventricular hemorrhage ,Fractional anisotropy ,Medicine ,Neurology (clinical) ,business ,Diffusion MRI ,Research Article - Abstract
Background and ObjectivesThe neurologic deficits of neonatal post-hemorrhagic hydrocephalus (PHH) have been linked to periventricular white matter injury. To improve understanding of PHH-related injury, diffusion basis spectrum imaging (DBSI) was applied in neonates, modeling axonal and myelin integrity, fiber density, and extrafiber pathologies. Objectives included characterizing DBSI measures in periventricular tracts, associating measures with ventricular size, and examining MRI findings in the context of postmortem white matter histology from similar cases.MethodsA prospective cohort of infants born very preterm underwent term equivalent MRI, including infants with PHH, high-grade intraventricular hemorrhage without hydrocephalus (IVH), and controls (very preterm [VPT]). DBSI metrics extracted from the corpus callosum, corticospinal tracts, and optic radiations included fiber axial diffusivity, fiber radial diffusivity, fiber fractional anisotropy, fiber fraction (fiber density), restricted fractions (cellular infiltration), and nonrestricted fractions (vasogenic edema). Measures were compared across groups and correlated with ventricular size. Corpus callosum postmortem immunohistochemistry in infants with and without PHH assessed intra- and extrafiber pathologies.ResultsNinety-five infants born very preterm were assessed (68 VPT, 15 IVH, 12 PHH). Infants with PHH had the most severe white matter abnormalities and there were no consistent differences in measures between IVH and VPT groups. Key tract-specific white matter injury patterns in PHH included reduced fiber fraction in the setting of axonal or myelin injury, increased cellular infiltration, vasogenic edema, and inflammation. Specifically, measures of axonal injury were highest in the corpus callosum; both axonal and myelin injury were observed in the corticospinal tracts; and axonal and myelin integrity were preserved in the setting of increased extrafiber cellular infiltration and edema in the optic radiations. Increasing ventricular size correlated with worse DBSI metrics across groups. On histology, infants with PHH had high cellularity, variable cytoplasmic vacuolation, and low synaptophysin marker intensity.DiscussionPHH was associated with diffuse white matter injury, including tract-specific patterns of axonal and myelin injury, fiber loss, cellular infiltration, and inflammation. Larger ventricular size was associated with greater disruption. Postmortem immunohistochemistry confirmed MRI findings. These results demonstrate DBSI provides an innovative approach extending beyond conventional diffusion MRI for investigating neuropathologic effects of PHH on neonatal brain development.
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- 2022
17. Democratizing produce waste reduction via hyperspectral imaging with low-cost home-built hyperspectral cameras
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Dhruv Darbha, James P McAllister, Dennis Dempsey, and Bonggu Shim
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We demonstrate that hyperspectral imaging with a home-built low-cost portable hyperspectral camera can predict the ripeness factor of vegetables or fruits. This research aids in democratizing reduction of produce waste at the consumer level.
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- 2022
18. The Effect of A1/A2 Reactive Astrocyte Expression on Hydrocephalus Shunt Failure
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Neena I. Marupudi, Jacob Gluski, Rooshan Arshad, David D. Limbrick, Diego M. Morales, Carolyn A. Harris, Fatemeh Khodadadei, and James P. McAllister
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education.field_of_study ,Pathology ,medicine.medical_specialty ,business.industry ,Population ,In situ hybridization ,medicine.disease ,Glial scar ,Hydrocephalus ,Gene expression profiling ,medicine.anatomical_structure ,Gene expression ,Medicine ,business ,education ,Shunt (electrical) ,Astrocyte - Abstract
Understanding the composition characteristics of the glial scar contributing to the high failure rate of neuroprosthetic devices implanted in the brain has been limited, to date, with the evaluation of cells, tissue, and biomarkers obstructing the implant. However, there remains a critical knowledge gap in gene expression profiles of the obstructing cells. This first-time study investigates the phenotypic expression specific to astrocyte scarring from those cells on hydrocephalus shunt surfaces at the time of failure, aimed at the development of therapeutic approaches to target reactive astrocytes for improved functional outcome. Recent evidence has indicated that the tissue obstructing shunts is over 80% inflammatory, with a more exaggerated astrocytic response. To understand how to mitigate the astrocyte immune response to shunts, we performed gene expression profiling of the C3 and EMP1 genes to quantify if astrocytes were classically activated and pro-inflammatory (A1) or alternatively activated and anti-inflammatory (A2), respectively. Shunt catheters were removed from patients at the time of failure and categorized by obstructed vs non-obstructed shunts. RNAscope fluorescent in situ hybridization and quantitative PCR analysis of the C3 and EMP1 expressed genes revealed that a heterogeneous mixed population of both the A1 and A2 reactive phenotype exist on the shunt surface. However, the number of A2 reactive astrocytes are significantly higher on obstructed shunts compared to A1 reactive astrocytes. ELISA data also confirmed higher levels of IL-6 for obstructed shunts involved in A2 reactive astrocyte proliferation and glial scar formation on the shunt surface. Since TNF-α and IL-1β propel resting astrocytes into an A2 reactive state, by simply blocking the secretion or action of these cytokines, astrocyte activation and attachment on obstructing shunts could be inhibited.
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- 2021
19. A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments
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Carolyn A. Harris, Leandro Castañeyra-Ruiz, Rebecca Golden, Alexis L. Hartman, Michael Talcott, Diego M. Morales, Ryan N. Dilger, Sarah H. Zwick, Stephen A. Fleming, David D. Limbrick, Maria Garcia-Bonilla, James P. McAllister, and Albert M. Isaacs
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Pathology ,medicine.medical_specialty ,Swine ,Shunt ,Ventriculoperitoneal Shunt ,Cellular and Molecular Neuroscience ,Cognition ,Developmental Neuroscience ,Medicine ,Animals ,RC346-429 ,Surgical treatment ,Kaolin ,business.industry ,Research ,Acquired hydrocephalus ,Age Factors ,General Medicine ,medicine.disease ,Magnetic Resonance Imaging ,Pathophysiology ,Shunt (medical) ,Hydrocephalus ,Animal models ,Acquired Hydrocephalus ,Disease Models, Animal ,medicine.anatomical_structure ,Neurology ,Cerebral cortex ,Ventriculomegaly ,Neurology. Diseases of the nervous system ,business - Abstract
Background Many animal models have been used to study the pathophysiology of hydrocephalus; most of these have been rodent models whose lissencephalic cerebral cortex may not respond to ventriculomegaly in the same way as gyrencephalic species and whose size is not amenable to evaluation of clinically relevant neurosurgical treatments. Fewer models of hydrocephalus in gyrencephalic species have been used; thus, we have expanded upon a porcine model of hydrocephalus in juvenile pigs and used it to explore surgical treatment methods. Methods Acquired hydrocephalus was induced in 33–41-day old pigs by percutaneous intracisternal injections of kaolin (n = 17). Controls consisted of sham saline-injected (n = 6) and intact (n = 4) animals. Magnetic resonance imaging (MRI) was employed to evaluate ventriculomegaly at 11–42 days post-kaolin and to plan the surgical implantation of ventriculoperitoneal shunts at 14–38-days post-kaolin. Behavioral and neurological status were assessed. Results Bilateral ventriculomegaly occurred post-induction in all regions of the cerebral ventricles, with prominent CSF flow voids in the third ventricle, foramina of Monro, and cerebral aqueduct. Kaolin deposits formed a solid cast in the basal cisterns but the cisterna magna was patent. In 17 untreated hydrocephalic animals. Mean total ventricular volume was 8898 ± 5917 SD mm3 at 11–43 days of age, which was significantly larger than the baseline values of 2251 ± 194 SD mm3 for 6 sham controls aged 45–55 days, (p Conclusions Kaolin induction of acquired hydrocephalus in juvenile pigs produced an in vivo model that is highly translational, allowing systematic studies of the pathophysiology and clinical treatment of hydrocephalus.
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- 2021
20. Acquired hydrocephalus is associated with neuroinflammation, progenitor loss, and cellular changes in the subventricular zone and periventricular white matter
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Maria Garcia-Bonilla, Leandro Castaneyra-Ruiz, Sarah Zwick, Michael Talcott, Ayodamola Otun, Albert M. Isaacs, Diego M. Morales, David D. Limbrick, and James P. McAllister
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Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Neurology ,Swine ,Lateral Ventricles ,Neuroinflammatory Diseases ,Animals ,Female ,General Medicine ,White Matter ,Cerebral Ventricles ,Hydrocephalus - Abstract
Background Hydrocephalus is a neurological disease with an incidence of 80–125 per 100,000 births in the United States. Neuropathology comprises ventriculomegaly, periventricular white matter (PVWM) alterations, inflammation, and gliosis. We hypothesized that hydrocephalus in a pig model is associated with subventricular and PVWM cellular alterations and neuroinflammation that could mimic the neuropathology described in hydrocephalic infants. Methods Hydrocephalus was induced by intracisternal kaolin injections in 35-day old female pigs (n = 7 for tissue analysis, n = 10 for CSF analysis). Age-matched sham controls received saline injections (n = 6). After 19–40 days, MRI scanning was performed to measure the ventricular volume. Stem cell proliferation was studied in the Subventricular Zone (SVZ), and cell death and oligodendrocytes were examined in the PVWM. The neuroinflammatory reaction was studied by quantifying astrocytes and microglial cells in the PVWM, and inflammatory cytokines in the CSF. Results The expansion of the ventricles was especially pronounced in the body of the lateral ventricle, where ependymal disruption occurred. PVWM showed a 44% increase in cell death and a 67% reduction of oligodendrocytes. In the SVZ, the number of proliferative cells and oligodendrocyte decreased by 75% and 57% respectively. The decrease of the SVZ area correlated significantly with ventricular volume increase. Neuroinflammation occurred in the hydrocephalic pigs with a significant increase of astrocytes and microglia in the PVWM, and high levels of inflammatory interleukins IL-6 and IL-8 in the CSF. Conclusion The induction of acquired hydrocephalus produced alterations in the PVWM, reduced cell proliferation in the SVZ, and neuroinflammation.
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- 2021
21. A multicenter retrospective study of heterogeneous tissue aggregates obstructing ventricular catheters explanted from patients with hydrocephalus
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Marc R. Del Bigio, James P. McAllister, Brandon G. Rocque, Jacob Gluski, David D. Limbrick, Prashant Hariharan, Jeffrey Sondheimer, Neena Marupudi, Carolyn A. Harris, Alexandra Petroj, Andrew Jea, Steven D. Ham, William E. Whitehead, Sandeep Sood, and University of Manitoba
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0301 basic medicine ,Catheter Obstruction ,Male ,Pathology ,Time Factors ,Ventriculoperitoneal Shunt ,0302 clinical medicine ,Cerebrospinal fluid ,Catheters, Indwelling ,Occlusion ,Child ,Multicenter ,Age Factors ,General Medicine ,medicine.anatomical_structure ,Neurology ,Child, Preschool ,Immunohistochemistry ,Choroid plexus ,Female ,Ependyma ,Hydrocephalus ,Adult ,medicine.medical_specialty ,Adolescent ,Lumen (anatomy) ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Young Adult ,Imaging, Three-Dimensional ,Developmental Neuroscience ,medicine ,Humans ,RC346-429 ,Retrospective Studies ,Biobank ,business.industry ,Research ,Infant ,Surgical outcomes ,Histology ,medicine.disease ,Retrospective cohort ,Shunt obstruction ,030104 developmental biology ,Choroid Plexus ,Neurology. Diseases of the nervous system ,Shunt failure ,business ,030217 neurology & neurosurgery - Abstract
Background Implantation of ventricular catheters (VCs) to drain cerebrospinal fluid (CSF) is a standard approach to treat hydrocephalus. VCs fail frequently due to tissue obstructing the lumen via the drainage holes. Mechanisms driving obstruction are poorly understood. This study aimed to characterize the histological features of VC obstructions and identify links to clinical factors. Methods 343 VCs with relevant clinical data were collected from five centers. Each hole on the VCs was classified by degree of tissue obstruction after macroscopic analysis. A subgroup of 54 samples was analyzed using immunofluorescent labelling, histology and immunohistochemistry. Results 61.5% of the 343 VCs analyzed had tissue aggregates occluding at least one hole (n = 211) however the vast majority of the holes (70%) showed no tissue aggregates. Mean age at which patients with occluded VCs had their first surgeries (3.25 yrs) was lower than in patients with non-occluded VCs (5.29 yrs, p Conclusion Our data show that age of the first surgery and length of time a VC is implanted are factors that influence the degree of VC obstruction. The tissue aggregates obstructing VCs are composed predominantly of astrocytes and macrophages; microglia have a relatively small presence.
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- 2021
22. Diffusion basis spectrum imaging in post-hemorrhagic hydrocephalus of prematurity
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James P. McAllister, Christopher D. Smyser, Sheng-Kwei Song, Leandro Castañeyra-Ruiz, Diego M. Morales, David D. Limbrick, Albert M. Isaacs, D. Sonika, Y. Yan, Jeffrey J. Neil, Ajit George, Haley E. Botteron, S. Peng, D. Alexopoulous, and Harri Merisaari
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Pathology ,medicine.medical_specialty ,biology ,business.industry ,medicine.disease ,Corpus callosum ,White matter ,Cellular infiltration ,Post-Hemorrhagic Hydrocephalus ,Myelin ,Intraventricular hemorrhage ,medicine.anatomical_structure ,Fractional anisotropy ,Synaptophysin ,biology.protein ,Medicine ,business - Abstract
ObjectiveThe debilitating neurological deficits of neonatal post-hemorrhagic hydrocephalus (PHH) have been linked to periventricular white matter injury. To improve understanding of the deleterious mechanisms underlying PHH-related brain injury, this study applied diffusion basis spectrum imaging (DBSI) for the first time in neonates, modeling white matter fibers to assess axonal and myelin integrity, fiber density, and extra-fiber pathologies including cellularity, edema, and inflammation. The objectives of the study were to characterize DBSI measures in key periventricular white matter tracts of PHH infants, associate those diffusion measures with ventricular size, and utilize postmortem white matter histology to compare with the MRI findings.MethodA prospective cohort of very preterm infants (n=95) underwent MRI at term equivalent age, of which 68 were controls (VPT group), 15 had high-grade intraventricular hemorrhage without hydrocephalus (IVH group), and 12 had PHH (PHH group). DBSI metrics extracted from manually segmented corpus callosum (CC), corticospinal tracts (CST), and optic radiations (OPRA) included fiber level axial diffusivity (FAD), fiber radial diffusivity (FRD), fiber fractional anisotropy (FFA), fiber fraction (FF), restricted fractions (RF), and non-restricted fractions (NRF). All measures were contrasted across groups and correlated with frontal occipital horn ratio (FOHR), a measure of ventricular size. Postmortem immunohistochemistry was performed on the CC of 10 preterm infants (five VPT, three IVH, and two PHH) and two full-term infants who died from non-neurologic causes assessing white matter intra- and extra-fiber pathologies, as well as the integrity of the adjoining ventricular and subventricular zones.ResultsExcept for FF in the CC, there were no differences in all measures between IVH and VPT infants. In the unmyelinated CC, PHH had the lowest FF, FAD, and FFA and the highest RF. In the CC, FOHR related negatively with FAD, FFA, and FF and positively with RF. In the myelinated CST, PHH had the lowest FAD, FFA, and FF and the highest FRD and RF. FOHR related negatively to FAD and FFA and positively with NRF and FRD. In the OPRA, PHH was associated with the lowest FF and the highest RF, NRF, and FAD. FOHR related positively with FAD and NRF and negatively with FF. On postmortem tissues, PHH was associated with the highest white matter cellularity counts, variable amounts of cytoplasmic vacuolation, and the lowest synaptophysin marker intensity. The adjoining ventricular and subventricular zones in PHH had poor cytoarchitecture on H&E staining and relatively increased expression of GFAP and IBA1.ConclusionsThis initial utilization of DBSI to investigate neonatal brain development and injury demonstrated that PHH was associated with diffuse periventricular white matter injury, with tract-specific microstructural patterns and severity of axonal injury, myelin injury, white matter fiber loss, hypercellularity, and inflammation. While axonal injury was present in the CST and unmyelinated CC, myelin injury occurred only in the CST. The OPRA predominantly showed inflammation with myelin preservation. White matter cellular infiltration occurred in all tracts. Postmortem immunohistochemistry confirmed the imaging findings of decreased axonal fiber density, sparser fiber architecture, and increased cellular infiltration. Larger ventricular size was associated with greater white matter disruption. Building upon these results, DBSI provides an innovative approach for investigating the complex neuropathological effects of PHH on periventricular white matter microstructure.
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- 2021
23. Glial Associated Impairment of the Glymphatic System in Experimental Neonatal Hydrocephalus
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Ramin Eskandari, Joseph Tyler Vasas, and James P. McAllister
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Pathology ,medicine.medical_specialty ,business.industry ,Medicine ,Glymphatic system ,business ,medicine.disease ,Hydrocephalus - Abstract
Background Changes in aquaporin-4 (AQP4) and glial fibrillary acid protein (GFAP) expression by astrocytes have been observed in several pathologies. It is hypothesized that prolonged exposure to pathologically elevated intracranial pressure (ICP) may be linked to impaired glymphatic pathways. In this study we explore histological consequences of prolonged pressure-induced injury in a feline model of neonatal hydrocephalus through changes in AQP4 and GFAP expression. We discuss the implications this may have in gaining a better understanding of the underlying mechanisms of hydrocephalus (HCP). Methods Using a neonatal feline model, obstructive HCP was induced through kaolin injection into the cisterna magna. Time between injection and intervention via ventricular reservoir placement was used to divide groups into early and late treatment groups. Early and late animals received reservoirs at 1- and 2-weeks post kaolin injection, respectively. Controls underwent sham operations (saline injection instead of kaolin). Animals were sacrificed at 4 months allowing for a chronic treated hydrocephalic model at time of brain harvest. Immunofluorescent staining for GFAP, AQP4 and DAPI was performed on histological brain sections from each group, and densitometry was used to quantify the relative signal of protein expression. Results Hydrocephalus was seen in all animals receiving kaolin injection as demonstrated by magnetic resonance imaging, clinical examination and neurological sequelae. Hydrocephalic animals demonstrated lower levels of perivascular AQP4 expression, increased diffuse AQP4 expression and increased glial scarring of perivascular, ependymal and subependymal spaces. Cerebral microvasculature of early treatment groups demonstrated increased astrocytic processes in the perivascular spaces, while late treatment groups demonstrated increased glial scar formation. Overall, the glymphatic system was severely disrupted in chronic treated hydrocephalus compared to controls. Conclusions Reactive astrogliosis and AQP4 mislocation are evident in early and late reservoir-treated HCP. Glial scarring in the perivascular, ependymal and subependymal spaces concurrent with AQP4 internalization from the perivascular region are prominent in HCP conditions present within the neonatal period. Delay in treatment by 1 week demonstrates quantifiable increases in perivascular and ependymal glial scarring at 4 months of age. Further investigation is needed to correlate glymphatic disruption with impaired CSF absorption and its role in promoting progressive hydrocephalus.
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- 2021
24. Analysis of N-acetyl cysteine modified polydimethylsiloxane shunt for improved treatment of hydrocephalus
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Jeff Horbatiuk, James P. McAllister, Carolyn A. Harris, Mira Zaranek, Pranav Gopalakrishnan, Andrea Dumitrescu, and Saja Al‐Saloum
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Materials science ,Catheters ,0206 medical engineering ,Biomedical Engineering ,Catheter Obstruction ,02 engineering and technology ,engineering.material ,Article ,Biomaterials ,Contact angle ,Coating ,Humans ,Dimethylpolysiloxanes ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,Cerebrospinal Fluid Shunts ,Acetylcysteine ,Surface coating ,Catheter ,engineering ,Surface modification ,Wetting ,0210 nano-technology ,Shunt (electrical) ,Biomedical engineering ,Hydrocephalus - Abstract
A major cause of hydrocephalus shunt failure is cell adhesion and obstruction of shunt catheter holes. An estimated 50% of pediatric shunts fail in the first 2 years of insertion, decreasing cell attachment and catheter obstruction can prolong the lifetime and effectiveness of the device. From previous studies, it was shown that treatment of the polydimethylsiloxane (PDMS) surface of a standard catheter with an N-acetyl-cysteine (NAC/1-ethyl-3-(3-dimethylanimopropyl)carbodiimide hydrochloride/N-hydroxysuccinimide) layer increases the wettability of the surface and has been shown to decrease cell adhesion. Other studies indicate that NAC's antioxidant behavior induces glutathione and in turn modulates cell inflammatory pathways. The current study explores the longevity of the NAC coating from the surface of the catheter over time and shows its effect on valve function. Using SEM imaging, contact angle testing, and nanodrop spectrophotometry, this release was quantified for shunt samples incubated for 0, 10, 30, 60, and 90 days. Contact angle showed a significant increase in wettability of the surface when shunts were treated with NAC, confirming successful surface modification. Pressure assays determined that if the coating is release it had no detrimental downstream effects, such as on the shunt valve mechanism. SEM imaging revealed slight deformations in surface coating indicative of salt deposition on the modified shunt samples, while nanodrop spectrophotometry and contact angle data trends suggested some discharge of the NAC coating from the catheter surfaces. The effects of NAC on cell activity may transform the way hydrocephalus is treated in the future by increasing the longevity of the shunt to protect from obstruction.
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- 2020
25. MR Elastography demonstrates reduced white matter shear stiffness in early-onset hydrocephalus
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Rick Abbott, James P. McAllister, Diego M. Morales, David D. Limbrick, J.T. Goodrich, S. Yang, Mark E. Wagshul, Andrew J. Kobets, W. Mowrey, and Avital Meiri
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CDI, Child’s Depression Inventory ,Logistic regression ,CSF, cerebrospinal fluid ,OSS, octahedral shear strain ,0302 clinical medicine ,IVH, Intraventricular hemorrhage ,SLCH, Saint Louis Children’s Hospital ,Depression (differential diagnoses) ,VVR, ventricular volume ratio ,medicine.diagnostic_test ,ANTs, Anatomical Normalization Tools ,05 social sciences ,Brain ,Regular Article ,Magnetic Resonance Imaging ,White Matter ,medicine.anatomical_structure ,MDEV, multi-frequency dual elasto-visco ,Neurology ,ICP, intracranial pressure ,Cardiology ,Elasticity Imaging Techniques ,MRE, Magnetic Resonance Elastography ,Female ,HOQ, hydrocephalus outcome questionnaire ,Elastography ,Headaches ,medicine.symptom ,Hydrocephalus ,Pediatric hydrocephalus ,Shear stiffness ,musculoskeletal diseases ,Quality of life ,medicine.medical_specialty ,animal structures ,Cognitive Neuroscience ,Computer applications to medicine. Medical informatics ,ETV, endoscopic third ventriculostomy ,WB, whole brain ,R858-859.7 ,macromolecular substances ,ICV, intracranial volume ,MR Elastography ,050105 experimental psychology ,White matter ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,0501 psychology and cognitive sciences ,Radiology, Nuclear Medicine and imaging ,WM, white matter ,RC346-429 ,Aged ,BDI, Beck’s Depression Inventory ,Shunting ,business.industry ,technology, industry, and agriculture ,Magnetic resonance imaging ,IQR, Interquartile range ,medicine.disease ,equipment and supplies ,QoL, quality of life ,Magnetic resonance elastography ,White matter stiffness ,Neurology. Diseases of the nervous system ,Neurology (clinical) ,DTI, diffusion tensor imaging ,business ,030217 neurology & neurosurgery - Abstract
Highlights • White matter stiffness is significantly reduced in stable, shunted hydrocephalus patients vs controls. • In patients, age, sex and ventricular volume have significant associations with brain stiffness. • Lower brain stiffness, but not ventricular volume, predicts worse quality of life and depression., Introduction Hydrocephalus that develops early in life is often accompanied by developmental delays, headaches and other neurological deficits, which may be associated with changes in brain shear stiffness. However, noninvasive approaches to measuring stiffness are limited. Magnetic Resonance Elastography (MRE) of the brain is a relatively new noninvasive imaging method that provides quantitative measures of brain tissue stiffness. Herein, we aimed to use MRE to assess brain stiffness in hydrocephalus patients compared to healthy controls, and to assess its associations with ventricular size, as well as demographic, shunt-related and clinical outcome measures. Methods MRE was collected at two imaging sites in 39 hydrocephalus patients and 33 healthy controls, along with demographic, shunt-related, and clinical outcome measures including headache and quality of life indices. Brain stiffness was quantified for whole brain, global white matter (WM), and lobar WM stiffness. Group differences in brain stiffness between patients and controls were compared using two-sample t-tests and multivariable linear regression to adjust for age, sex, and ventricular volume. Among patients, multivariable linear or logistic regression was used to assess which factors (age, sex, ventricular volume, age at first shunt, number of shunt revisions) were associated with brain stiffness and whether brain stiffness predicts clinical outcomes (quality of life, headache and depression). Results Brain stiffness was significantly reduced in patients compared to controls, both unadjusted (p ≤ 0.002) and adjusted (p ≤ 0.03) for covariates. Among hydrocephalic patients, lower stiffness was associated with older age in temporal and parietal WM and whole brain (WB) (beta (SE): −7.6 (2.5), p = 0.004; −9.5 (2.2), p = 0.0002; −3.7 (1.8), p = 0.046), being female in global and frontal WM and WB (beta (SE): −75.6 (25.5), p = 0.01; −66.0 (32.4), p = 0.05; −73.2 (25.3), p = 0.01), larger ventricular volume in global, and occipital WM (beta (SE): −11.5 (3.4), p = 0.002; −18.9 (5.4), p = 0.0014). Lower brain stiffness also predicted worse quality of life and a higher likelihood of depression, controlling for all other factors. Conclusions Brain stiffness is reduced in hydrocephalus patients compared to healthy controls, and is associated with clinically-relevant functional outcome measures. MRE may emerge as a clinically-relevant biomarker to assess the neuropathological effects of hydrocephalus and shunting, and may be useful in evaluating the effects of therapeutic alternatives, or as a supplement, of shunting.
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- 2020
26. Call for Collaboration: Characterization of a Multicenter Hydrocephalus Shunt Biobank
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James P. McAllister, Sandeep Sood, Steven D. Ham, Amanda Morgan, Jacob Gluski, David D. Limbrick, Prashant Hariharan, Neena Marupudi, Carolyn A. Harris, Andrew Jea, William E. Whitehead, Paul Zajciw, and Diego M. Morales
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medicine.medical_specialty ,business.industry ,Medicine ,business ,medicine.disease ,Biobank ,Shunt (medical) ,Hydrocephalus ,Surgery - Abstract
Background Pediatric hydrocephalus is a devastating and costly disease. The mainstay of treatment is still surgical shunting of cerebrospinal fluid (CSF). These shunts fail at a high rate and impose a significant burden on patients, their families and society. The relationship between clinical decision making and shunt failure is poorly understood and multifaceted, but catheter occlusion remains the most frequent cause of shunt complications. In order to investigate factors that affect shunt failure, we have established the Wayne State University (WSU) shunt biobank.Methods To date, six hospital centers have contributed various components of failed shunts and CSF from patients diagnosed with hydrocephalus at a young age. The hardware samples are transported in paraformaldehyde and transferred to phosphate-buffered saline with sodium azide upon deposit into the biobank. Once in the bank, they are then available for study. Informed consent is obtained by the local center before corresponding clinical data are entered into a REDCap database. All data are entered under a coded identifier. Collaborators may then correlate biologic findings against the clinical database.Results 295 shunt samples were collected from 228 patients starting from May 2015 to September 2019. Patients with multiple samples in the bank provide a unique opportunity to study longitudinal changes in disease. With the clinical data alone, we saw a significant difference in the number of revisions per patient between centers (Kruskal-Wallis H test, p-value= 0.000022). There was no significant difference between the distributions of hydrocephalus etiologies between centers, and the leading etiology at all centers was post-hemorrhagic hydrocephalus.Conclusion Hospital center and patient recruitment for the biobank is ongoing. The biobank will yield insights for future collaborators, allow centers to benchmark their performance, and offer a unique-longitudinal perspective on the pathology of this lifelong condition. Future work will expand on the contribution of different site-specific and patient-specific factors to identify potential cause and effect relationships.
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- 2020
27. Blood Exposure Causes Ventricular Zone Disruption and Glial Activation In Vitro
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Albert M. Isaacs, Steven L. Brody, James P. McAllister, David D. Limbrick, Diego M. Morales, Sonika Dahiya, Jennifer Strahle, and Leandro Castañeyra-Ruiz
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Male ,0301 basic medicine ,Radioimmunoprecipitation Assay ,Pathology ,medicine.medical_specialty ,Ependymal Cell ,Cell ,In Vitro Techniques ,Cell junction ,Cerebral Ventricles ,Pathology and Forensic Medicine ,Adherens junction ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Organ Culture Techniques ,Glial Fibrillary Acidic Protein ,medicine ,Animals ,Humans ,Cerebral Intraventricular Hemorrhage ,Caspase 3 ,Cadherin ,business.industry ,Original Articles ,General Medicine ,Cadherins ,medicine.disease ,Neural stem cell ,Astrogliosis ,Mice, Inbred C57BL ,Disease Models, Animal ,Blood ,Intercellular Junctions ,030104 developmental biology ,medicine.anatomical_structure ,Animals, Newborn ,Neurology ,Neurology (clinical) ,Ependyma ,business ,Neuroglia ,Hydrocephalus - Abstract
Intraventricular hemorrhage (IVH) is the most common cause of pediatric hydrocephalus in North America but remains poorly understood. Cell junction-mediated ventricular zone (VZ) disruption and astrogliosis are associated with the pathogenesis of congenital, nonhemorrhagic hydrocephalus. Recently, our group demonstrated that VZ disruption is also present in preterm infants with IVH. On the basis of this observation, we hypothesized that blood triggers the loss of VZ cell junction integrity and related cytopathology. In order to test this hypothesis, we developed an in vitro model of IVH by applying syngeneic blood to cultured VZ cells obtained from newborn mice. Following blood treatment, cells were assayed for N-cadherin-dependent adherens junctions, ciliated ependymal cells, and markers of glial activation using immunohistochemistry and immunoblotting. After 24–48 hours of exposure to blood, VZ cell junctions were disrupted as determined by a significant reduction in N-cadherin expression (p
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- 2018
28. Opportunities in posthemorrhagic hydrocephalus research: outcomes of the Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop
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Richard F. Keep, Jill A. Morris, James P. McAllister, Jenna E. Koschnitzky, Yun C. Yung, Jennifer Strahle, and David D. Limbrick
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congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,education ,Review ,Brain damage ,lcsh:RC346-429 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Developmental Neuroscience ,Posthemorrhagic hydrocephalus ,Animals ,Humans ,Medicine ,030212 general & internal medicine ,Intensive care medicine ,Premature ,lcsh:Neurology. Diseases of the nervous system ,Cerebral Hemorrhage ,Clinical Trials as Topic ,business.industry ,Posthemorrhagic ,General Medicine ,Research opportunities ,Congresses as Topic ,medicine.disease ,Hydrocephalus ,nervous system diseases ,Intraventricular hemorrhage ,Germinal matrix hemorrhage ,Neurology ,Blood brain barrier ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
The Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop was held on July 25 and 26, 2016 at the National Institutes of Health. The workshop brought together a diverse group of researchers including pediatric neurosurgeons, neurologists, and neuropsychologists with scientists in the fields of brain injury and development, cerebrospinal and interstitial fluid dynamics, and the blood–brain and blood–CSF barriers. The goals of the workshop were to identify areas of opportunity in posthemorrhagic hydrocephalus research and encourage scientific collaboration across a diverse set of fields. This report details the major themes discussed during the workshop and research opportunities identified for posthemorrhagic hydrocephalus. The primary areas include (1) preventing intraventricular hemorrhage, (2) stopping primary and secondary brain damage, (3) preventing hydrocephalus, (4) repairing brain damage, and (5) improving neurodevelopment outcomes in posthemorrhagic hydrocephalus.
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- 2018
29. Call for Collaboration: Characterization of a Multicenter Hydrocephalus Shunt Biobank
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Gluski, Jacob, primary, Zajciw, Paul, additional, Hariharan, Prashant, additional, Morgan, Amanda, additional, Morales, Diego, additional, Jea, Andrew, additional, Whitehead, William, additional, Marupudi, Neena, additional, Ham, Steven, additional, Sood, Sandeep, additional, II, James P. McAllister, additional, Limbrick, David D., additional, and Harris, Carolyn, additional
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- 2020
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30. Next generation of ventricular catheters for hydrocephalus based on parametric designs
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José M. Amigó, Ulrich-W. Thomale, Roberto Gazzeri, Martin U. Schuhmann, James P. McAllister, Marcelo Galarza, and Ángel Giménez
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medicine.medical_specialty ,Catheter Obstruction ,Pulsatile flow ,Computational fluid dynamics ,Cerebral Ventricles ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Catheters, Indwelling ,0302 clinical medicine ,Shear stress ,Humans ,Medicine ,Parametric statistics ,business.industry ,Equipment Design ,General Medicine ,Mechanics ,medicine.disease ,Cerebrospinal Fluid Shunts ,Surgery ,Hydrocephalus ,Catheter ,Flow (mathematics) ,Pediatrics, Perinatology and Child Health ,Hydrodynamics ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
The flow pattern of the cerebrospinal fluid is probably the most important factor related to obstruction of ventricular catheters during the normal treatment of hydrocephalus. To better comprehend the flow pattern, we have carried out a parametric study via numerical models of ventricular catheters. In previous studies, the flow was studied under steady and, recently, in pulsatile boundary conditions by means of computational fluid dynamics (CFD) in three-dimensional catheter models. This study aimed to bring in prototype models of catheter CFD flow solutions as well to introduce the theory behind parametric development of ventricular catheters. A preceding study allowed deriving basic principles which lead to designs with improved flow patterns of ventricular catheters. The parameters chosen were the number of drainage segments, the distances between them, the number and diameter of the holes on each segment, as well as their relative angular position. CFD results of previously unreleased models of ventricular catheter flow solutions are presented in this study. Parametric development guided new designs with better flow distribution while lowering the shear stress of the catheters holes. High-resolution 3D printed catheter solutions of three models and basic benchmark testing are introduced as well. The next generation of catheter with homogeneous flow patterns based on parametric designs may represent a step forward for the treatment of hydrocephalus, by possibly broadening their lifespan.
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- 2017
31. Cerebrospinal Fluid Biomarkers of Pediatric Hydrocephalus
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Leandro Castañeyra-Ruiz, David D. Limbrick, Daniel R. Berger, James P. McAllister, Roland H. Han, and Diego M. Morales
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0301 basic medicine ,medicine.medical_specialty ,Physical examination ,Infant, Premature, Diseases ,Pediatrics ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Cerebrospinal fluid ,Neuroimaging ,medicine ,Humans ,Intensive care medicine ,Cerebral Hemorrhage ,Cerebrospinal Fluid ,medicine.diagnostic_test ,business.industry ,Infant, Newborn ,Infant ,General Medicine ,medicine.disease ,Hydrocephalus ,030104 developmental biology ,Intraventricular hemorrhage ,Anesthesia ,Pediatrics, Perinatology and Child Health ,Quality of Life ,Biomarker (medicine) ,Surgery ,Neurology (clinical) ,business ,Biomarkers ,030217 neurology & neurosurgery ,Pediatric hydrocephalus - Abstract
Hydrocephalus (HC) is a common, debilitating neurological condition that requires urgent clinical decision-making. At present, neurosurgeons rely heavily on a patient's history, physical examination findings, neuroimaging, and clinical judgment to make the diagnosis of HC or treatment failure (e.g., shunt malfunction). Unfortunately, these tools, even in combination, do not eliminate subjectivity in clinical decisions. In order to improve the management of infants and children with HC, there is an urgent need for new biomarkers to complement currently available tools and enable clinicians to confidently establish the diagnosis of HC, assess therapeutic efficacy/treatment failure, and evaluate current and future developmental challenges, so that every child has access to the resources they need to optimize their outcome and quality of life.
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- 2017
32. A Novel Experimental Animal Model of Adult Chronic Hydrocephalus
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Tito Vivas-Buitrago, Daniele Rigamonti, Barbara J. Crain, James P. McAllister, Daniel A. Herzka, Jiadi Xu, Oscar Gonzalez-Perez, Ari M. Blitz, Mikhail V. Pletnikov, Hugo Guerrero-Cazares, Eric W. Sankey, Ignacio Jusué-Torres, Alicia Hulbert, Lee H. Jeon, Jennifer Lu, Alfredo Quinones-Hinojosa, and Joshua Crawford
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Asymptomatic ,Subarachnoid Space ,Muscle hypertrophy ,Rats, Sprague-Dawley ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Normal pressure hydrocephalus ,medicine ,Animals ,Kaolin ,Gait ,Inflammation ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,medicine.disease ,Fibrosis ,Magnetic Resonance Imaging ,Hydrocephalus, Normal Pressure ,Rats ,Hydrocephalus ,Radiography ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Cerebral hemisphere ,Female ,Surgery ,Neurology (clinical) ,Subarachnoid space ,medicine.symptom ,business ,Locomotion ,030217 neurology & neurosurgery ,Ventriculomegaly - Abstract
Background The pathogenesis of adult chronic hydrocephalus is not fully understood, and the temporal relationship between development of the radiological changes and neurological deterioration is unknown. Objective To clarify the progression of radiological-histological changes and subsequent clinical manifestations of adult chronic hydrocephalus. Methods Kaolin was injected bilaterally into the subarachnoid space overlying the cranial convexities in 20 adult rats. Magnetic resonance imaging (MRI) was obtained by using an 11.7 T scanner at 14, 60, 90, and 120 days after kaolin injection. Locomotor, gait, and cognitive evaluations were performed independently. Kaolin distribution and the associated inflammatory and fibrotic responses were histologically analyzed. Results Evans index of ventriculomegaly showed significant progressive growth in ventricular size over all time points examined. The greatest enlargement occurred within the first 2 months. Evans index also correlated with the extent of kaolin distribution by MRI and by pathological examination at all time points. First gait changes occurred at 69 days, anxiety at 80, cognitive impairment at 81, and locomotor difficulties after 120 days. Only locomotor deterioration was associated with Evans index or the radiological evaluation of kaolin extension. Inflammatory/fibrotic response was histologically confirmed over the cranial convexities in all rats, and its extension was associated with ventricular size and with the rate of ventricular enlargement. Conclusion Kaolin injected into the subarachnoid space over the cerebral hemispheres of adult rats produces an inflammatory/fibrotic response leading in a slow-onset communicating hydrocephalus that is initially asymptomatic. Increased ventricular size eventually leads to gait, memory, and locomotor impairment closely resembling the course of human adult chronic hydrocephalus. Abbreviation NPH, normal pressure hydrocephalus.
- Published
- 2016
33. Experimental Hydrocephalus
- Author
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James P. McAllister
- Subjects
Pathology ,medicine.medical_specialty ,Study methods ,Neuroimaging ,business.industry ,In vivo ,medicine ,medicine.disease ,business ,Hydrocephalus - Published
- 2019
34. Feasibility of fast brain diffusion MRI to quantify white matter injury in pediatric hydrocephalus
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Christopher D. Smyser, Robert C. McKinstry, David D. Limbrick, Joshua S. Shimony, Alexis L. Hartman, Jennifer Strahle, Albert M. Isaacs, Matthew D. Smyth, Leandro Castañeyra-Ruiz, James P. McAllister, Yan Yan, Madison Cook, and Diego M. Morales
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Genu of the corpus callosum ,business.industry ,Sedation ,White Matter Injury ,General Medicine ,medicine.disease ,Article ,030218 nuclear medicine & medical imaging ,Hydrocephalus ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Image acquisition ,Abnormality ,medicine.symptom ,Nuclear medicine ,business ,030217 neurology & neurosurgery ,Pediatric hydrocephalus ,Diffusion MRI - Abstract
OBJECTIVETraditionally, diffusion MRI (dMRI) has been performed in parallel with high-resolution conventional MRI, which requires long scan times and may require sedation or general anesthesia in infants and young children. Conversely, fast brain MRI permits image acquisition without the need for sedation, although its short pulse sequences, susceptibility to motion artifact, and contrast resolution have limited its use to assessing ventricular size or major structural variations. Here, the authors demonstrate the feasibility of leveraging a 3-direction fast brain MRI protocol to obtain reliable dMRI measures.METHODSFast brain MRI with 3-direction dMRI was performed in infants and children before and after hydrocephalus treatment. Regions of interest in the posterior limbs of the internal capsules (PLICs) and the genu of the corpus callosum (gCC) were drawn on diffusion-weighted images, and mean diffusivity (MD) data were extracted. Ventricular size was determined by the frontal occipital horn ratio (FOHR). Differences between and within groups pre- and posttreatment, and FOHR-MD correlations were assessed.RESULTSOf 40 patients who met inclusion criteria (median age 27.5 months), 15 (37.5%), 17 (42.5%), and 8 (20.0%) had posthemorrhagic hydrocephalus (PHH), congenital hydrocephalus (CH), or no intracranial abnormality (controls), respectively. A hydrocephalus group included both PHH and CH patients. Prior to treatment, the FOHR (p < 0.001) and PLIC MD (p = 0.027) were greater in the hydrocephalus group than in the controls. While the mean gCC MD in the hydrocephalus group (1.10 × 10−3 mm2/sec) was higher than that of the control group (0.98), the difference was not significant (p = 0.135). Following a median follow-up duration of 14 months, decreases in FOHR, PLIC MD, and gCC MD were observed in the hydrocephalus group and were similar to those in the control group (p = 0.107, p = 0.702, and p = 0.169, respectively). There were no correlations identified between FOHR and MDs at either time point.CONCLUSIONSThe utility of fast brain MRI can be extended beyond anatomical assessments to obtain dMRI measures. A reduction in PLIC and gCC MD to levels similar to those of controls was observed within 14 months following shunt surgery for hydrocephalus in PHH and CH infants. Further studies are required to assess the role of fast brain dMRI for assessing clinical outcomes in pediatric hydrocephalus patients.
- Published
- 2018
35. Lumbar Cerebrospinal Fluid Biomarkers of Posthemorrhagic Hydrocephalus of Prematurity: Amyloid Precursor Protein, Soluble Amyloid Precursor Protein α, and L1 Cell Adhesion Molecule
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David M. Holtzman, Terrie E. Inder, Shawgi A. Silver, Diego M. Morales, James P. McAllister, Clinton D. Morgan, Michael Wallendorf, Deanna Mercer, David D. Limbrick, and Rakesh Rao
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Male ,medicine.medical_specialty ,L1 ,Neural Cell Adhesion Molecule L1 ,Infant, Premature, Diseases ,Sensitivity and Specificity ,Gastroenterology ,Article ,Amyloid beta-Protein Precursor ,03 medical and health sciences ,0302 clinical medicine ,Cerebrospinal fluid ,030225 pediatrics ,Internal medicine ,Odds Ratio ,medicine ,Amyloid precursor protein ,Humans ,CSF albumin ,Cerebral Hemorrhage ,biology ,business.industry ,Cell adhesion molecule ,Infant, Newborn ,medicine.disease ,Pathophysiology ,Logistic Models ,Intraventricular hemorrhage ,biology.protein ,Female ,Surgery ,Neural cell adhesion molecule ,Neurology (clinical) ,business ,Biomarkers ,Infant, Premature ,030217 neurology & neurosurgery ,Hydrocephalus - Abstract
BACKGROUND Intraventricular hemorrhage (IVH) is the most frequent, severe neurological complication of prematurity and is associated with posthemorrhagic hydrocephalus (PHH) in up to half of cases. PHH requires lifelong neurosurgical care and is associated with significant cognitive and psychomotor disability. Cerebrospinal fluid (CSF) biomarkers may provide both diagnostic information for PHH and novel insights into its pathophysiology. OBJECTIVE To explore the diagnostic ability of candidate CSF biomarkers for PHH. METHODS Concentrations of amyloid precursor protein (APP), soluble APPα (sAPPα), soluble APPβ, neural cell adhesion molecule-1 (NCAM-1), L1 cell adhesion molecule (L1CAM), tau, phosphorylated tau, and total protein (TP) were measured in lumbar CSF from neonates in 6 groups: (1) no known neurological disease (n = 33); (2) IVH grades I to II (n = 13); (3) IVH grades III to IV (n = 12); (4) PHH (n = 12); (5) ventricular enlargement without hydrocephalus (n = 10); and (6) hypoxic ischemic encephalopathy (n = 13). CSF protein levels were compared using analysis of variance, and logistic regression was performed to examine the predictive ability of each marker for PHH. RESULTS Lumbar CSF levels of APP, sAPPα, L1CAM, and TP were selectively increased in PHH compared with all other conditions (all P < .001). The sensitivity, specificity, and odds ratios of candidate CSF biomarkers for PHH were determined for APP, sAPPα, and L1CAM; cut points of 699, 514, and 113 ng/mL yielded odds ratios for PHH of 80.0, 200.0, and 68.75, respectively. CONCLUSION Lumbar CSF APP, sAPPα, L1CAM, and TP were selectively increased in PHH. These proteins, and sAPPα, in particular, hold promise as biomarkers of PHH and provide novel insight into PHH-associated neural injury and repair.
- Published
- 2016
36. Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus
- Author
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Mohamed Gabir, Clinton D. Morgan, Diego M. Morales, Gakwaya Habiyaremye, James P. McAllister, Deanna Mercer, Brandon S. Baksh, David D. Limbrick, Rowland H. Han, and Travis S. CreveCoeur
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Chemokine ,Post-hemorrhagic ,medicine.medical_treatment ,CSF ,Infant, Premature, Diseases ,lcsh:RC346-429 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Post-Hemorrhagic Hydrocephalus ,0302 clinical medicine ,Cerebrospinal fluid ,Developmental Neuroscience ,Preterm ,Internal medicine ,Humans ,Medicine ,lcsh:Neurology. Diseases of the nervous system ,Neuroinflammation ,Cerebral Intraventricular Hemorrhage ,Hematology ,biology ,business.industry ,Research ,Infant, Newborn ,General Medicine ,Pathophysiology ,030104 developmental biology ,Cytokine ,Endocrinology ,Spinal Cord ,Neurology ,biology.protein ,Encephalitis ,Cytokines ,Biomarker (medicine) ,Female ,Inflammation Mediators ,Chemokines ,Prematurity ,business ,Biomarkers ,Infant, Premature ,030217 neurology & neurosurgery ,Hydrocephalus - Abstract
Background Neuroinflammation has been implicated in the pathophysiology of post-hemorrhagic hydrocephalus (PHH) of prematurity, but no comprehensive analysis of signaling molecules has been performed using human cerebrospinal fluid (CSF). Methods Lumbar CSF levels of key cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF-β1, IFN-γ) and chemokines (XCL-1, CCL-2, CCL-3, CCL-19, CXCL-10, CXCL-11, CXCL-12) were measured using conventional and multiplexed Enzyme-linked Immunosorbent Assays and compared between preterm infants with PHH and those with no known neurological injury. The relationships between individual biomarker levels and specific CSF cell counts were examined. Results Total protein (TP) CSF levels were elevated in the PHH subjects compared to controls. CSF levels of IL-1α, IL-4, IL-6, IL-12, TNF-α, CCL-3, CCL-19, and CXCL-10 were significantly increased in PHH whereas XCL-1 was significantly decreased in PHH. When normalizing by TP, IL-1α, IL-1β, IL-10, IL-12, CCL-3, and CCL-19 levels were significantly elevated compared to controls, while XCL-1 levels remained significantly decreased. Among those with significantly different levels in both absolute and normalized levels, only absolute CCL-19 levels showed a significant correlation with CSF nucleated cells, neutrophils, and lymphocytes. IL-1β and CXCL-10 also were correlated with total cell count, nucleated cells, red blood cells, and neutrophils. Conclusions Neuroinflammation is likely to be an important process in the pathophysiology of PHH. To our knowledge, this is the first study to investigate CSF levels of chemokines in PHH as well as the only one to show XCL-1 selectively decreased in a diseased state. Additionally, CCL-19 was the only analyte studied that showed significant differences between groups and had significant correlation with cell count analysis. The selectivity of CCL-19 and XCL-1 should be further investigated. Future studies will further delineate the role of these cytokines and chemokines in PHH.
- Published
- 2017
37. Neuroimaging of white matter abnormalities in pediatric hydrocephalus
- Author
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Francesco T. Mangano, Weihong Yuan, and James P. McAllister
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Pathology ,medicine.medical_specialty ,Internal capsule ,business.industry ,Corpus callosum ,medicine.disease ,Hydrocephalus ,White matter ,medicine.anatomical_structure ,Neuroimaging ,Corona radiata ,Pediatrics, Perinatology and Child Health ,Fractional anisotropy ,medicine ,Radiology, Nuclear Medicine and imaging ,Neurology (clinical) ,business ,Diffusion MRI - Abstract
Hydrocephalus (HCP) is a severe pathologic condition in which the ventricular system enlarges in response to abnor- mal cerebrospinal fluid production and absorption mechanisms. While accumulating evidence implicates damage to various white matter (WM) structures as one of the major neurobiological mechanisms underlying poor behavioral outcomes in children with HCP, current evaluation of such damage remains limited. Diffusion tensor imaging (DTI) is a unique magnetic resonance technique that exploits differences in the diffusion properties of water molecules in different tissue. Anisotropic diffusion prop- erties, as measured by DTI, are strongly influenced by the micro-structural components of WM and thus can help to assess the properties in tissue constituents, tissue microstructure and cytoarchitecture. Initial clinical studies have shown that DTI is a sen- sitive imaging tool for investigating WM damage as well as the extent of recovery in HCP. A key study has shown that the periventricular WM and corona radiata in children between 12-18 years exhibited increased pre-operative fractional anisotropy (FA) driven by a slightly increased axial diffusivity and a more dramatic decreased radial diffusivity. Post-operatively the FA in these regions returned to normal in most patients. In contrast, the corpus callosum was found to have low FA pre-operatively which did not respond to cerebrospinal fluid diversion surgery. A more recent study reported a similar lower FA and higher mean diffusivity in the corpus callosum in infants. However, the abnormalities in the internal capsule were found to be more heterogeneous. Longitudinal study showed that most DTI measurements returned to normal post-operatively. In experimental studies, similar abnormalities in DTI were found in both neonatal and infantile rats with induced HCP. These findings correlated with increased astrocyte and microglial reactivity and reduced myelination. This review also discusses interpretations regarding the different patterns of DTI abnormalities seen in HCP in different WM regions. Overall, support is growing for DTI as a useful non-invasive imaging tool in the diagnosis and treatment of pediatric hydrocephalus.
- Published
- 2015
38. Abstracts from Hydrocephalus 2016
- Author
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Jamie Hoffberger, Karin Kockum, I. Jusué Torres, Fernando Hakim, M. Kang, David Cohen, Kemel A. Ghotme, Maria Kojoukhova, Armelle Lokossou, Juan Fernando Ramón, Jamie Robison, M. Vallejo, Otto Lilja-Lund, Anne M. Remes, Fredrik Lundin, Carlo Emanuel Petitto, Samir A Matloob, P. Sharkey, U. Kehler, Mark G. Luciano, A. Sattar, Shaokoon Cheng, M. Ishikawa, P. Saavedra, Tito Vivas-Buitrago, M. Flores, M. Schmid Daners, Hannah M. Tully, Juliana Benevenuto Tornai, Mahdi Asgari, Jussi Mattila, L. Mahieu, S. Foley, Lynne E. Bilston, Simon Garnotel, Jennifer Lu, Diane de Zélicourt, M. Hammad, Anders Eklund, Norman R. Relkin, Heimo Viinamäki, D. Moran, Stéphanie Salmon, David D. Limbrick, K. A. Carson, Ville E. Korhonen, J. A. Buttner-Ennever, S. D. Thompson, Nicolás Useche, D. Baghawatti, Ville Leinonen, Pierre Payoux, S. Mori, Eric A. Schmidt, S. Zuspan, Manuel Gehlen, Ossi Nerg, William G. Bradley, Daniel F. Hanley, D. M. Morales, K Onouchi, A. J. Luikku, W. Arouk, Rachel Dlugash, Seppo Helisalmi, M. A. Patel, L. D. Thorne, Anette Hall, C. García, Simon D Thompson, Paulo Cesar Modesto, M. W. Mancini, Abanti Sanyal, Gayane Yenokyan, L. Gray, Hugh F. Smisson, Mitja I. Kurki, Manoel Jacobsen Teixeira, Anne M Koivisto, S. Naqvi, P. Mayorga, Franz Marie Cruz, Deborah A Sival, C. Martinez, Joe Sam Robinson, Mikko Hiltunen, M. Mora, Debayan Dasgupta, Carmel Curtis, A. Buitrago, Gabriel André da Silva Mendes, M. Garzon, Laurent Balardy, K. Yamamoto, D. Kawaguchi, Vartan Kurtcuoglu, Anne Christine Januel, A. Hung, Eduardo Ortega, A. Häyrinen, Gregory James, Ari M. Blitz, Claudia Craven, T. Bach, P. Gantet, Jyrki Lötjönen, M. Timonen, Esteban M. Rodríguez, Mark G. Hamilton, L. D. Watkins, James P. McAllister, Ehud J. Schmidt, L. Murcia, V. Sousa, Andreas Eleftheriou, K. Carson, Fernando Campos Gomes Pinto, Heather Katzen, I. Jurjević, P. Haylock Vize, Masakazu Miyajima, Bryn A. Martin, Joshua Crawford, Zofia Czosnyka, D. Gomez, L. Al-Mutawa, Daniele Rigamonti, B. Bezerra, Benjamin D. Elder, M. A. Sevestre, P. Dutra, M. Jumaly, Gwenaël Pagé, K. Rigamonti, I. Moreno, Irina Alafuzoff, Monserrat Guerra, S. Yasar, H. A. Soto, Ahmed K Toma, D. Thompson, Irene Baudracco, Heinke Pülhorn, C. G. Valêncio, Eric W. Sankey, Walter A. Kukull, Harri Sintonen, Olivier Balédent, Alice Pong, H. Treviño, R. Jose, G. Calia, M. F. Oliveira, M. Dawood, Quoc Anh Thai, Karin Vío, A. J. Remolina, R. H. Maykot, Daniel A. Herzka, Arun Chandran, M. F. Cárdenas, Mikhail V. Pletnikov, Sanna-Kaisa Herukka, Lars Söderström, C. R. Goodwin, Jiadi Xu, Noam Alperin, Marcie R. Williams, K. Aquilina, K. Takagi, Maryoris Jara, K. Maitani, L. Almeida-Lopes, Christophe Cognard, K. Karagiozov, Alejandro P. Adam, Sonia Bermúdez, Katrine Riklund, Fabienne Ory-Magne, A. Guenego, T. Belcher, M. Zitoun, Diego Ernesto Lira González, Hugo Guerrero-Cazares, Eino Solje, Jussi Paananen, O. Omoush, Hisayuki Murai, Toshimasa Shin, M. A. Grijalba, Nelly Fabre, David Solomon, Sara Rodríguez, K. J. Whitehouse, K. I. Vanha, S. S. S. Silvestre, P. Tall, Juha E. Jääskeläinen, Per Hellström, H. Al-Ghamdi, Petra M. Klinge, Elna-Marie Larsson, Juan Armando Mejía, Richard J. Edwards, Jan Malm, Francis Loth, A. Rigamonti, Joel Huovinen, Ikuko Ogino, Antti J. Luikku, V. Eslami, Chihiro Akiba, Wendy C. Ziai, S. Yamada, Rodolfo Casimiro Reis, W. B. Dobyns, M. C. Matiz, Anna Sutela, Katarina Laurell, J. S. Davidson, Montserrat Guerra, Lauriane Jugé, Abhay Moghekar, A. S. Rao, Ritva Vanninen, K. Sandhu, Kostas N. Fountas, Hajime Arai, G. Clemens, D. Riveros, Dan Doherty, J. Wemmer, Richard Holubkov, S. Vakili, Risto P. Roine, Madoka Nakajima, T. L. Wenger, Saman Nekoovaght-Tak, Karl Bechter, Antti Junkkari, Antonio J. Jiménez, Nichol McBee, Catherine McMahon, D. da Vigua, L. Domínguez, Tuomas Rauramaa, M. J. Fritsch, Jaana Rummukainen, N. Badran, M. Maghaslah, Hilkka Soininen, Alfredo Quiñones-Hinojosa, Effie Z. Kapsalaki, Lewis Thorne, Université Catholique de Louvain = Catholic University of Louvain (UCL), Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516 (LASIRE), Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Inönü University, Silicon Nanoelectronics Photonics and Structures (SiNaps), PHotonique, ELectronique et Ingénierie QuantiqueS (PHELIQS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHirurgie, IMagerie et REgénération tissulaire de l’extrémité céphalique - Caractérisation morphologique et fonctionnelle - UR UPJV 7516 (CHIMERE), Université de Picardie Jules Verne (UPJV), and CHU Amiens-Picardie
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Pediatrics ,medicine.medical_specialty ,business.industry ,[SDV]Life Sciences [q-bio] ,010401 analytical chemistry ,MEDLINE ,General Medicine ,medicine.disease ,01 natural sciences ,Meeting Abstracts ,lcsh:RC346-429 ,0104 chemical sciences ,Hydrocephalus ,Cellular and Molecular Neuroscience ,Text mining ,Developmental Neuroscience ,Neurology ,Medicine ,business ,lcsh:Neurology. Diseases of the nervous system ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2017
39. Cerebrospinal fluid biomarkers of infantile congenital hydrocephalus
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Terrie E. Inder, Brandon S. Baksh, David M. Holtzman, Jennifer Strahle, Diego M. Morales, James P. McAllister, Gakwaya Habiyaremye, David D. Limbrick, Michael Wallendorf, Clinton D. Morgan, and Deanna Mercer
- Subjects
0301 basic medicine ,Central Nervous System ,Male ,Pathology ,Aging ,Neurology ,Physiology ,lcsh:Medicine ,Neurological disorder ,Pathology and Laboratory Medicine ,Gastroenterology ,Nervous System ,Biochemistry ,Families ,Amyloid beta-Protein Precursor ,0302 clinical medicine ,Cerebrospinal fluid ,Medicine and Health Sciences ,lcsh:Science ,Child ,Children ,CSF albumin ,Cerebrospinal Fluid ,Stenosis ,Multidisciplinary ,Pathophysiology ,3. Good health ,Body Fluids ,Aquaporin 4 ,Female ,Anatomy ,Infants ,Research Article ,Hydrocephalus ,medicine.medical_specialty ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,Internal medicine ,medicine ,Congenital Disorders ,Humans ,business.industry ,lcsh:R ,Infant, Newborn ,Biology and Life Sciences ,Infant ,Odds ratio ,medicine.disease ,030104 developmental biology ,Age Groups ,People and Places ,lcsh:Q ,Population Groupings ,business ,030217 neurology & neurosurgery ,Biomarkers - Abstract
Introduction Hydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value. Methods CSF levels of amyloid precursor protein (APP) and derivative isoforms (sAPPα, sAPPβ, Aβ42), tau, phosphorylated tau (pTau), L1CAM, NCAM-1, aquaporin 4 (AQP4), and total protein (TP) were measured by ELISA in 20 children with CHC. Two comparative groups were included: age-matched controls and children with other neurological diseases. Demographic parameters, ventricular frontal-occipital horn ratio, associated brain malformations, genetic alterations, and surgical treatments were recorded. Logistic regression analysis and receiver operating characteristic curves were used to examine the association of each CSF protein with CHC. Results CSF levels of APP, sAPPα, sAPPβ, Aβ42, tau, pTau, L1CAM, and NCAM-1 but not AQP4 or TP were increased in untreated CHC. CSF TP and normalized L1CAM levels were associated with FOR in CHC subjects, while normalized CSF tau levels were associated with FOR in control subjects. Predictive ability for CHC was strongest for sAPPα, especially in subjects ≤12 months of age (p
- Published
- 2017
40. Differential vulnerability of white matter structures to experimental infantile hydrocephalus detected by diffusion tensor imaging
- Author
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Cameron A. Mason, James P. McAllister, Kelley E. Lloyd, Ramin Eskandari, Amanda N. Oeschle, and Osama Abdullah
- Subjects
medicine.medical_specialty ,Pathology ,Time Factors ,Internal capsule ,Optic tract ,Optic chiasm ,Corpus callosum ,Nerve Fibers, Myelinated ,Statistics, Nonparametric ,Corpus Callosum ,White matter ,Internal Capsule ,Internal medicine ,Fractional anisotropy ,Image Processing, Computer-Assisted ,medicine ,Animals ,Optic Tract ,business.industry ,Brain ,General Medicine ,medicine.disease ,Magnetic Resonance Imaging ,White Matter ,Hydrocephalus ,Disease Models, Animal ,Diffusion Tensor Imaging ,medicine.anatomical_structure ,Animals, Newborn ,Optic Chiasm ,Pediatrics, Perinatology and Child Health ,Cats ,Cardiology ,Anisotropy ,Neurology (clinical) ,business ,Diffusion MRI - Abstract
The differential vulnerability of white matter (WM) to acute and chronic infantile hydrocephalus and the related effects of early and late reservoir treatment are unknown, but diffusion tensor imaging (DTI) could provide this information. Thus, we characterized WM integrity using DTI in a clinically relevant model. Obstructive hydrocephalus was induced in 2-week-old felines by intracisternal kaolin injection. Ventricular reservoirs were placed 1 (early) or 2 (late) weeks post-kaolin and tapped frequently based solely on neurological deficit. Hydrocephalic and age-matched control animals were sacrificed 12 weeks postreservoir. WM integrity was evaluated in the optic system, corpus callosum, and internal capsule prereservoir and every 3 weeks using DTI. Analyses were grouped as acute (
- Published
- 2014
41. Kaolin‐induced ventriculomegaly at weaning produces long‐term learning, memory, and motor deficits in rats
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Charles V. Vorhees, Amanda A. Braun, James P. McAllister, Francesco T. Mangano, Michael T. Williams, Weihong Yuan, Diana M. Lindquist, and Robyn M. Amos-Kroohs
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Male ,Movement disorders ,medicine.medical_treatment ,Morris water navigation task ,Weaning ,Cisterna magna ,Article ,Rats, Sprague-Dawley ,Cerebrospinal fluid ,Developmental Neuroscience ,medicine ,Animals ,Kaolin ,Maze Learning ,Saline ,Prepulse inhibition ,Memory Disorders ,Movement Disorders ,Learning Disabilities ,Mental Disorders ,medicine.disease ,Rats ,Hydrocephalus ,Disease Models, Animal ,Anesthesia ,Chronic Disease ,medicine.symptom ,Psychology ,Developmental Biology ,Ventriculomegaly - Abstract
Ventriculomegaly occurs when there is imbalance between creation and absorption of cerebrospinal fluid (CSF); even when treated, long-term behavioral changes occur. Kaolin injection in the cisterna magna of rats produces an obstruction of CSF outflow and models one type of hydrocephalus. Previous research with this model shows that neonatal onset has mixed effects on Morris water maze (MWM) and motoric performance; we hypothesized that this might be because the severity of ventricular enlargement was not taken into consideration. In the present experiment, rats were injected with kaolin or saline on postnatal day (P)21 and analyzed in subgroups based on Evan's ratios (ER) of the severity of ventricular enlargement at the end of testing to create 4 subgroups from least to most severe: ER0.4–0.5, ER0.51-0.6, ER0.61-0.7, and ER0.71-0.82, respectively. Locomotor activity (dry land and swimming), acoustic startle with prepulse inhibition (PPI), and MWM performance were tested starting on P28 (122 cm maze) and again on P42 (244 cm maze). Kaolin-treated animals weighed significantly less than controls at all times. Differences in locomotor activity were seen at P42 but not P28. On P28 there was an increase in PPI for all but the least severe kaolin-treated group, but no difference at P42 compared with controls. In the MWM at P28, all kaolin-treated groups had longer path lengths than controls, but comparable swim speeds. With the exception of the least severe group, probe trial performance was worse in the kaolin-treated animals. On P42, only the most severely affected kaolin-treated group showed deficits compared with control animals. This group showed no MWM learning and no memory for the platform position during probe trial testing. Swim speed was unaffected, indicating motor deficits were not responsible for impaired learning and memory. These findings indicate that kaolin-induced ventriculomegaly in rats interferes with cognition regardless of the final enlargement of the cerebral ventricles, but final size critically determines whether lasting locomotor, learning, and memory impairments occur.
- Published
- 2014
42. Use of quantitative 16S rRNA PCR to determine bacterial load does not augment conventional cerebrospinal fluid (CSF) cultures among children undergoing treatment for CSF shunt infection
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Jay Riva-Cambrin, Brian Van Yserloo, Judy A. Daly, Kevin E. Nelson, Randy L. Jensen, David L. Gillespie, Tamara D. Simon, James P. McAllister, Chris Stockmann, and Anne J. Blaschke
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Microbiology (medical) ,Microbiological culture ,Adolescent ,Real-Time Polymerase Chain Reaction ,Shunt ,Article ,law.invention ,Microbiology ,03 medical and health sciences ,Cerebrospinal fluid ,law ,RNA, Ribosomal, 16S ,Humans ,Cerebrospinal ,Child ,Children ,Polymerase chain reaction ,Cerebrospinal Fluid ,030304 developmental biology ,0303 health sciences ,Bacteria ,biology ,030306 microbiology ,Bacterial Infections ,General Medicine ,16S ribosomal RNA ,biology.organism_classification ,Bacterial Load ,Cerebrospinal Fluid Shunts ,Anti-Bacterial Agents ,3. Good health ,Infectious Diseases ,Real-time polymerase chain reaction ,Sample collection ,Infection ,Shunt (electrical) - Abstract
The aim of this study was to develop a quantitative 16S rRNA assay for determination of bacterial nucleic acid load in cerebrospinal fluid (CSF) shunt infection and to compare quantitative 16S rRNA polymerase chain reaction (PCR) findings to those of conventional bacterial culture in patients treated for CSF shunt infection. We developed a quantitative 16S rRNA PCR assay that detected bacterial load across a range of 2.5 × 109 down to 2.5 × 104 16S copies/mL CSF under experimental conditions for numerous Gram-positive and Gram-negative organisms. However, when applied to archived CSF samples from 25 shunt infection episodes, correlations between positive bacterial culture and 16S rRNA levels were seen in only half of infections, and 16S rRNA levels dropped precipitously after an initial peak on the first day of sample collection. Bacterial load measured using 16S rRNA PCR does not provide sufficient information beyond bacterial culture to inform CSF shunt infection treatment.
- Published
- 2014
43. Effect of delayed intermittent ventricular drainage on ventriculomegaly and neurological deficits in experimental neonatal hydrocephalus
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Ramin Eskandari, Eric C. Burdett, James P. McAllister, and Melissa Packer
- Subjects
medicine.medical_specialty ,Time Factors ,Cerebral Ventricles ,medicine ,Animals ,cardiovascular diseases ,Kaolin ,Adverse effect ,Neurologic Examination ,medicine.diagnostic_test ,business.industry ,Ventricular drainage ,Magnetic resonance imaging ,General Medicine ,medicine.disease ,Magnetic Resonance Imaging ,Hydrocephalus ,Disease Models, Animal ,Animals, Newborn ,Delayed intervention ,Motor Skills ,Anesthesia ,Pediatrics, Perinatology and Child Health ,Cerebral ventricle ,Cats ,Linear Models ,cardiovascular system ,Drainage ,Neurology (clinical) ,Neurosurgery ,Nervous System Diseases ,business ,Ventriculomegaly - Abstract
Evidence-based guidelines do not indicate when ventricular reservoirs should be placed in children with neonatal hydrocephalus, and delayed intervention is common. We hypothesize that delayed ventricular drainage has adverse effects on structural development and functional outcomes.Using a well-established animal model of kaolin-induced obstructive hydrocephalus, we evaluated neurologic deficit after early (~1 week post-kaolin) or late (~2 weeks post-kaolin) placement of ventricular reservoirs which were tapped according to strict neurologic criteria.Progressive ventriculomegaly was similar in early- and late-reservoir implantation groups. The average neurologic deficit scores (NDSs) over the experimental period were 0 (n=6), 2.74 (n=5), and 2.01 (n=3) for the control, early-, and late-reservoir groups, respectively. At reservoir placement, early-group animals displayed enlarged ventricles without neurologic deficits (mean NDS=0.17), while the late group displayed ventriculomegaly with clinical signs of hydrocephalus (mean NDS=3.13). The correlation between ventriculomegaly severity and NDS in the early group was strongly positive in the acute (before surgery to 3 weeks post-reservoir placement) (R(2)=0.65) and chronic (6 to 12 weeks post-reservoir placement) (R(2)=0.65) phases, while the late group was less correlated (acute R(2)=0.51; chronic R(2)=0.19).Current practice favors delaying reservoir implantation until signs of elevated intracranial pressure and neurologic deficit appear. Our results demonstrate that animals in early and late groups undergo the same course of ventriculomegaly. The findings also show that tapping reservoirs in these neonatal hydrocephalic animals based on neurologic deficit does not halt progressive ventricular enlargement and that neurologic deficit correlates strongly with ventricular enlargement.
- Published
- 2012
44. What We Should Know About the Cellular and Tissue Response Causing Catheter Obstruction in the Treatment of Hydrocephalus
- Author
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Carolyn A. Harris and James P. McAllister
- Subjects
medicine.medical_specialty ,Surgical strategy ,business.industry ,Catheter Obstruction ,medicine.disease ,Cerebrospinal Fluid Shunts ,Ventricular catheter ,Surgery ,Hydrocephalus ,Shunting ,Catheter ,Catheters, Indwelling ,Postoperative Complications ,Cerebrospinal fluid ,medicine ,Humans ,Equipment Failure ,Neurology (clinical) ,business ,Shunt (electrical) - Abstract
The treatment of hydrocephalus by cerebrospinal fluid shunting is plagued by ventricular catheter obstruction. Shunts can become obstructed by cells originating from tissue normal to the brain or by pathological cells in the cerebrospinal fluid for a variety of reasons. In this review, the authors examine ventricular catheter obstruction and identify some of the modifications to the ventricular catheter that may alter the mechanical and chemical cues involved in obstruction, including alterations to the surgical strategy, modifications to the chemical surface of the catheter, and changes to the catheter architecture. It is likely a combination of catheter modifications that will improve the treatment of hydrocephalus by prolonging the life of ventricular catheters to improve patient outcome.
- Published
- 2012
45. A cell junction pathology of neural stem cells leads to abnormal neurogenesis and hydrocephalus
- Author
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Jaime Jaque, Wilfred F. A. den Dunnen, Antonio J. Jiménez, Maria Montserrat Guerra, Maria Clara Jara, María Dolores Domínguez-Pinos, José Manuel Pérez-Fígares, Eduardo Ortega, Francisco Guerra, James P. McAllister, Cesar Gonzalez, Rosa I. Muñoz, Luis Federico Bátiz, Karin Vío, Deborah A Sival, Sara Rodríguez, Esteban M. Rodríguez, Alexander Ortloff, Conrad E. Johanson, and Molecular Neuroscience and Ageing Research (MOLAR)
- Subjects
CONGENITAL HYDROCEPHALUS ,Pathology ,medicine.medical_specialty ,SUBVENTRICULAR ZONE ,Neurogenesis ,Subventricular zone ,PERIVENTRICULAR NODULAR HETEROTOPIA ,GAP-JUNCTION ,EMBRYONIC CEREBROSPINAL-FLUID ,Biology ,Gene mutation ,abnormal neurogenesis ,stem cell transplantation ,INJURED SPINAL-CORD ,General Biochemistry, Genetics and Molecular Biology ,Cerebral Ventricles ,Precursor cell ,Neurosphere ,CEREBRAL-CORTEX ,medicine ,Animals ,Humans ,lcsh:QH301-705.5 ,ALPHA-SNAP ,Cell Proliferation ,neural stem cells ,Cerebral Aqueduct ,Cell Differentiation ,General Medicine ,H-TX RAT ,Embryonic stem cell ,Neural stem cell ,Rats ,Intercellular Junctions ,medicine.anatomical_structure ,lcsh:Biology (General) ,nervous system ,NEURONAL MIGRATION ,General Agricultural and Biological Sciences ,Ependyma ,hydrocephalus ,Neuroscience - Abstract
Most cells of the developing mammalian brain derive from the ventricular (VZ) and the subventricular (SVZ) zones. The VZ is formed by the multipotent radial glia/neural stem cells (NSCs) while the SVZ harbors the rapidly proliferative neural precursor cells (NPCs). Evidence from human and animal models indicates that the common history of hydrocephalus and brain maldevelopment starts early in embryonic life with disruption of the VZ and SVZ. We propose that a "cell junction pathology" involving adherent and gap junctions is a final common outcome of a wide range of gene mutations resulting in proteins abnormally expressed by the VZ cells undergoing disruption. Disruption of the VZ during fetal development implies the loss of NSCs whereas VZ disruption during the perinatal period implies the loss of ependyma. The process of disruption occurs in specific regions of the ventricular system and at specific stages of brain development. This explains why only certain brain structures have an abnormal development, which in turn results in a specific neurological impairment of the newborn. Disruption of the VZ of the Sylvian aqueduct (SA) leads to aqueductal stenosis and hydrocephalus, while disruption of the VZ of telencephalon impairs neurogenesis. We are currently investigating whether grafting of NSCs/neurospheres from normal rats into the CSF of hydrocephalic mutants helps to diminish/repair the outcomes of VZ disruption.
- Published
- 2012
46. Neocortical Capillary Flow Pulsatility is Not Elevated in Experimental Communicating Hydrocephalus
- Author
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Mark E. Wagshul, James P. McAllister, Yiting Yu, and Shams Rashid
- Subjects
medicine.medical_specialty ,Capillary action ,Pulsatile flow ,Pulsatility index ,Rats, Sprague-Dawley ,Cerebral circulation ,Cerebrospinal fluid ,Internal medicine ,medicine ,Animals ,Communicating hydrocephalus ,business.industry ,Brain ,Capillaries ,Rats ,Microscopy, Fluorescence, Multiphoton ,Endocrinology ,Neurology ,Pulsatile Flow ,Cerebral aqueduct ,Female ,Original Article ,Neurology (clinical) ,Animal studies ,Cardiology and Cardiovascular Medicine ,business ,Hydrocephalus - Abstract
While communicating hydrocephalus (CH) is often characterized by increased pulsatile flow of cerebrospinal fluid (CSF) in the cerebral aqueduct, a clear-cut explanation for this phenomenon is lacking. Increased pulsatility of the entire cerebral vasculature including the cortical capillaries has been suggested as a causative mechanism. To test this theory, we used two-photon microscopy to measure flow pulsatility in neocortical capillaries 40 to 500 μm below the pial surface in adult rats with CH at 5 to 7 days (acute, n=8) and 3 to 5 weeks (chronic, n=5) after induction compared with intact controls ( n=9). Averaging over all cortical depths, no increase in capillary pulsatility occurred in acute (pulsatility index (PI): 0.15±0.06) or chronic (0.14±0.05) CH animals compared with controls (0.18±0.07; P=0.07). More specifically, PI increased significantly with cortical depth in controls ( r=0.35, P
- Published
- 2011
47. Does drainage hole size influence adhesion on ventricular catheters?
- Author
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James P. McAllister and Carolyn A. Harris
- Subjects
genetic structures ,Mice ,Catheters, Indwelling ,Cell Adhesion ,Shear stress ,Animals ,Medicine ,Cell adhesion ,Hole size ,High rate ,business.industry ,Macrophages ,Equipment Design ,General Medicine ,Anatomy ,Cerebrospinal Fluid Shunts ,Ventricular catheter ,Rats ,Catheter ,Equipment failure ,Astrocytes ,Pediatrics, Perinatology and Child Health ,Equipment Failure ,Neurology (clinical) ,business ,Shunt (electrical) ,Biomedical engineering - Abstract
Ventricular catheter drainage holes of shunt systems used to treat hydrocephalus obstruct with tissue commonly comprising monocytes/macrophages, astrocytes, and giant cells. Despite high rates of obstruction, very few studies have manipulated drainage hole orientation, number, position, or diameter. By altering the hole diameter but maintaining a constant hole surface area, we manipulated shear stress through the holes, which we hypothesized would change the degree of macrophage and astrocyte attachment. First, a hole fabrication method was chosen from two fabrication techniques including punched holes in catheter tubing and constructed holes using nanofabrication techniques. Punched holes were chosen to vary hole size from 282 to 975 μm because (1) samples were geometrically similar to commercially available ventricular catheters without significant microscopic differences in roughness values and (2) total macrophage and astrocyte adhesion on the punched holes was not significantly different from adhesion on the commercially available catheters. Overall adhesion from least to most adherent appeared to follow 975
- Published
- 2011
48. Reactive astrocytosis, microgliosis and inflammation in rats with neonatal hydrocephalus
- Author
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Jennifer Forsyth, Osama Abdullah, Kelley E Deren, Brett Milash, James P. McAllister, Melissa Packer, and Edward W. Hsu
- Subjects
Pathology ,medicine.medical_specialty ,Blotting, Western ,Gene Expression ,Apoptosis ,Inflammation ,Biology ,Microgliosis ,Cerebral Ventricles ,Rats, Sprague-Dawley ,Central nervous system disease ,Developmental Neuroscience ,Pregnancy ,medicine ,Animals ,Gliosis ,Neuroinflammation ,Microglia ,Microarray Analysis ,medicine.disease ,Immunohistochemistry ,Magnetic Resonance Imaging ,Pathophysiology ,Rats ,Hydrocephalus ,medicine.anatomical_structure ,Animals, Newborn ,Neurology ,Cytokines ,Encephalitis ,Female ,Astrocytosis ,medicine.symptom - Abstract
The deleterious effects of hydrocephalus, a disorder that primarily affects children, include reactive astrocytosis, microgliosis and inflammatory responses; however, the roles that these mechanisms play in the pathophysiology of hydrocephalus are still not clear in terms of cytopathology and gene expression. Therefore we have examined neuroinflammation at both the cellular and the molecular levels in an experimental model of neonatal obstructive hydrocephalus. On post-natal day 1, rats received an intracisternal injection of kaolin to induce hydrocephalus; control animals received saline injections. Prior to sacrifice on post-natal day 22, animals underwent magnetic resonance imaging to quantify ventricular enlargement, and the parietal cortex was harvested for analysis. Immunohistochemistry and light microscopy were performed on 5 hydrocephalic and 5 control animals; another set of 5 hydrocephalic and 5 control animals underwent molecular testing with Western blots and a gene microarray. Scoring of immunoreactivity on a 4-point ranking scale for GFAP and Iba-1 demonstrated an increase in reactive astrocytes and reactive microglia respectively in the hydrocephalic animals compared to controls (2.90±0.11 vs. 0.28±0.26; 2.91±0.11 vs. 0.58±0.23, respectively). Western blots confirmed these results. Microarray analysis identified significant (1.5-fold) changes in 1729 of 33,951 genes, including 26 genes out of 185 genes (26/185) in the cytokine-cytokine receptor interaction pathway, antigen processing and presentation pathways (15/66), and the apoptosis pathway (10/69). Collectively, these results demonstrate alterations in normal physiology and an up-regulation of the inflammatory response. These findings lead to a better understanding of neonatal hydrocephalus and begin to form a baseline for future treatments that may reverse these effects.
- Published
- 2010
49. Mechanical contributions to astrocyte adhesion using a novel in vitro model of catheter obstruction
- Author
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Carolyn A. Harris, Candice Moon, James P. McAllister, Richard A. West, Eric Hudson, and James H. Resau
- Subjects
medicine.medical_specialty ,Indoles ,Catheter Obstruction ,Pulsatile flow ,Statistics, Nonparametric ,Catheterization ,Bioreactors ,Cerebrospinal fluid ,Developmental Neuroscience ,Glial Fibrillary Acidic Protein ,Cell Adhesion ,medicine ,Animals ,Cell adhesion ,business.industry ,Brain ,Adhesion ,Embryo, Mammalian ,medicine.disease ,Biomechanical Phenomena ,Rats ,Surgery ,Hydrocephalus ,Catheter ,Neurology ,Astrocytes ,Pulsatile Flow ,Stress, Mechanical ,business ,Shunt (electrical) ,Biomedical engineering - Abstract
Drainage and diversion of cerebrospinal fluid (CSF) through shunt systems is the most common treatment for hydrocephalus, but complications due to tissue obstruction of the catheter occur in up to 61% of patients. Although shunt systems have undergone limited technological advancements to resist mammalian cell adhesion, there is a need to further reduce adhesion that can exacerbate obstruction. The high intrinsic variability in clinical studies and an inability to predict chronic adhesion of host cells in vitro while maintaining the environmental conditions observed in hydrocephalus have impeded progress. We designed the hydrocephalus shunt catheter bioreactor (HSCB) to measure inflammatory cell adhesion under experimentally manipulated conditions of CSF pressure, pulsation rate, and flow rates. For a 20-h period, astrocytes were perfused through the pulsatile flow system, and adhesion on silicone catheters was recorded. These results were compared with those obtained under static cell culture conditions. Astrocyte adhesion was significantly increased under conditions of increased flow rate (0.25 and 0.30 mL/min), and a trend toward increased adhesion was observed under conditions of elevated pressure and pulsation rate. Because the HSCB represents physiologic conditions more accurately than static cell culture, our results suggest that standard static cell culturing techniques are insufficient to model inflammatory cell adhesion on catheters used in the treatment of hydrocephalus and that changes to the ventricular microenvironment can alter the mechanisms of cellular adhesion. The HSCB represents a relevant test system and is an effective model system for the analysis of cellular adhesion and occlusion of shunt catheters.
- Published
- 2010
50. Ventricular Zone Disruption in Human Neonates With Intraventricular Hemorrhage
- Author
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Wilfred F. A. den Dunnen, James P. McAllister, Maria Montserrat Guerra, Antonio J. Jiménez, Esteban M. Rodríguez, David D. Limbrick, Deborah A Sival, Robert E. Schmidt, Leandro Castaneyra Ruiz, Dolores Domínguez-Pinos, Diego M. Morales, Molecular Neuroscience and Ageing Research (MOLAR), and Movement Disorder (MD)
- Subjects
0301 basic medicine ,Male ,NEURAL STEM-CELLS ,Cerebral Ventricles ,Cerebrospinal fluid ,Neural Stem Cells ,Lateral Ventricles ,Ultrasonography ,Brain ,General Medicine ,Anatomy ,Immunohistochemistry ,Neural stem cell ,medicine.anatomical_structure ,Intraventricular hemorrhage ,Neurology ,Choroid plexus ,Female ,Autopsy ,Erratum ,Ependyma ,Ventricular zone ,Hydrocephalus ,BIRTH-WEIGHT INFANTS ,CONGENITAL HYDROCEPHALUS ,SUBVENTRICULAR ZONE ,Subventricular zone ,Neuroimaging ,Posthemorrhagic hydrocephalus ,Pathology and Forensic Medicine ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,CEREBROSPINAL-FLUID ,PRETERM INFANTS ,medicine ,Subependymal zone ,Humans ,Cerebral Hemorrhage ,Neural stem cells ,business.industry ,Infant, Newborn ,Infant ,Original Articles ,RADIAL GLIAL-CELLS ,medicine.disease ,030104 developmental biology ,nervous system ,Astrocytes ,CHOROID-PLEXUS ,HUMAN FETAL EPENDYMA ,Neurology (clinical) ,business ,Ventriculomegaly - Abstract
To determine if ventricular zone (VZ) and subventricular zone (SVZ) alterations are associated with intraventricular hemorrhage (IVH) and posthemorrhagic hydrocephalus, we compared postmortem frontal and subcortical brain samples from 12 infants with IVH and 3 nonneurological disease controls without hemorrhages or ventriculomegaly. Birth and expiration estimated gestational ages were 23.0-39.1 and 23.7-44.1 weeks, respectively; survival ranges were 0-42 days (median, 2.0 days). Routine histology and immunohistochemistry for neural stem cells (NSCs), neural progenitors (NPs), multiciliated ependymal cells (ECs), astrocytes (AS), and cell adhesion molecules were performed. Controls exhibited monociliated NSCs and multiciliated ECs lining the ventricles, abundant NPs in the SVZ, and medial vs. lateral wall differences with a complex mosaic organization in the latter. In IVH cases, normal VZ/SVZ areas were mixed with foci of NSC and EC loss, eruption of cells into the ventricle, cytoplasmic transposition of N-cadherin, subependymal rosettes, and periventricular heterotopia. Mature AS populated areas believed to be sites of VZ disruption. The cytopathology and extension of the VZ disruption correlated with developmental age but not with brain hemorrhage grade or location. These results corroborate similar findings in congenital hydrocephalus in animals and humans and indicate that VZ disruption occurs consistently in premature neonates with IVH.
- Published
- 2017
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