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BACKGROUND: The lesions besides lateral ventricle and motor recovery following rehabilitation have hardly been studied. OBJECTIVE: To explore the relationship between the size, location of infarction beside the lateral ventricle and motor recovery following rehabilitation. METHODS: A prospective cohort of 55 patients submitted to a Rehabilitation Medical Center between January 2015 and June 2019 who suffered a single cerebral infarction beside the lateral ventricle were included in the study. The size and distance between the posterior margin and the frontal-middle line (FML) of the lesion were measured. Follow-up was conducted until the recovery was no longer progressing. Barthel index and Brunstrom stages were used to evaluate the outcome (full recovery, partial recovery and poor recovery). Variance analysis and nonparametric test were used for the comparison between groups. Multivariate logistic regression analysis was used to screen the factors affecting the outcomes. The Pearson correlation coefficient was used to compare the volume of infarction, behind the FML and the outcomes. RESULTS: Among the 55 patients, the outcome was full recovery (n = 28), partial recovery (n = 13) and poor recovery (n = 14). Multivariate logistic regression analysis showed that volume and location of the infarction were significantly correlated with the outcome (p = 0.039, 0.050). The lesion volume in the full recovery patients was significantly smaller than that in the poor recovery patients (p

Ventricular drainage remains a usual but challenging procedure for neurosurgical trainees. The objective of the study was to describe reliable skin landmarks for ideal entry points (IEPs) to catheterize brain ventricles via frontal and parieto-occipital approaches.We included 30 subjects who underwent brain MRI and simulated the ideal catheterization trajectories of lateral ventricles using anterior and posterior approaches and localized skin surface IEPs. The optimal frontal target was the interventricular foramen and that for the parieto-occipital approach was the atrium. We measured the distances between these IEPs and easily identifiable skin landmarks.The frontal IEP was localized to 116.8 ± 9.3 mm behind the nasion on the sagittal plane and to 39.7 ± 4.9 mm lateral to the midline on the coronal plane. The ideal catheter length was estimated to be 68.4 ± 6.4 mm from the skin surface to the interventricular foramen. The parieto-occipital point was localized to 62.9 ± 7.4 mm above the ipsilateral tragus on the coronal plane and to 53.1 ± 9.1 mm behind the tragus on the axial plane. The ideal catheter length was estimated to be 48.3 ± 9.6 mm.The IEP for the frontal approach was localized to 11 cm above the nasion and 4 cm lateral to the midline. The IEP for the parieto-occipital approach was 5.5 cm behind and 6 cm above the tragus. These measurements lightly differ from the classical descriptions of Kocher's point and Keen's point and seem relevant to neurosurgical practice while using an orthogonal insertion.

In the past decade it has become evident that neuroblasts continue to supply the human cortex with interneurons via unique migratory streams shortly following birth. Owing to the size of the human brain, these newborn neurons must migrate long distances through complex cellular landscapes to reach their final locations. This process is poorly understood, largely because of technical difficulties in acquiring and studying neurotypical postmortem human samples along with diverging developmental features of well-studied mouse models. We reasoned that migratory streams of neuroblasts utilize cellular substrates, such as blood vessels, to guide their trek from the subventricular zone to distant cortical targets. Here, we evaluate the association between young interneuronal migratory streams and their preferred cellular substrates in gyrencephalic piglets during the developmental equivalent of human birth, infancy, and toddlerhood. US National Institutes of Health [R15NS108183] Published version ACKNOWLEDGMENTS We gratefully thank Drs. Sherrie Clark-Deener and Calvin Lau for their assistance with veterinary services. We are also thankful to Jessica Neary and Garrett Walker for assistance in animal husband-ry. We also would like to thank Raymundo Hernandez, Beatriz Torres, Swagatika Paul, and Dr. Alicia Pickrell for technical advice. We would like to acknowledge Karen Hall and Rachel McNeil for animal care. This work was supported by the US National Institutes of Health (R15NS108183 to P.D.M.) .

Ciliary motility disorders are known to cause hydrocephalus. The instantaneous velocity of cerebrospinal fluid (CSF) flow is dominated by artery pulsation, and it remains unclear why ciliary dysfunction results in hydrocephalus. In this study, we investigated the effects of cilia-induced surface velocity on CSF flow using computational fluid dynamics. A geometric model of the human ventricles was constructed using medical imaging data. The CSF produced by the choroid plexus and cilia-induced surface velocity were given as the velocity boundary conditions at the ventricular walls. We developed healthy and reduced cilia motility models based on experimental data of cilia-induced velocity in healthy wild-type and Dpcd-knockout mice. The results indicate that there is almost no difference in intraventricular pressure between healthy and reduced cilia motility models. Additionally, it was found that newly produced CSF from the choroid plexus did not spread to the anterior and inferior horns of the lateral ventricles in the reduced cilia motility model. These findings suggest that a ciliary motility disorder could delay CSF exchange in the anterior and inferior horns of the lateral ventricles.

Topoisomerase IIA (TOP2a) has traditionally been known as an important nuclear enzyme that resolves entanglements and relieves torsional stress of DNA double strands. However, its function in genomic transcriptional regulation remains largely unknown, especially during adult neurogenesis. Here, we show that TOP2a is preferentially expressed in neurogenic niches in the brain of adult mice, such as the subventricular zone (SVZ). Conditional knockout of Top2a in adult neural stem cells (NSCs) of the SVZ significantly inhibits their self-renewal and proliferation, and ultimately reduces neurogenesis. To gain insight into the molecular mechanisms by which TOP2a regulates adult NSCs, we perform RNA-sequencing (RNA-Seq) plus chromatin immunoprecipitation sequencing (ChIP-Seq) and identify ubiquitin-specific protease 37 (Usp37) as a direct TOP2a target gene. Importantly, overexpression of Usp37 is sufficient to rescue the impaired self-renewal ability of adult NSCs caused by Top2a knockdown. Taken together, this proof-of-principle study illustrates a TOP2a/Usp37-mediated novel molecular mechanism in adult neurogenesis, which will significantly expand our understanding of the function of topoisomerase in the adult brain.

We present a case series of 7 patients with intraventricular arachnoid cysts of lateral ventricle managed with endoscopic treatment with proposed classification of the cyst based on anatomic extent.In all patients, the lateral ventricle arachnoid cyst was primarily located in the trigone and body of the lateral ventricle. Proposed classification is based on extension of the arachnoid cyst. Type 1 is an arachnoid cyst located in the lateral ventricle only, type 2 is a lateral ventricle arachnoid cyst extending to the quadrigeminal cistern, and type 3 is the lateral ventricle arachnoid cyst extending to the velum interpositum cistern.Two patients were managed with multiple fenestration and septostomy, and in 1 patient where the cyst was not adherent to the ventricular wall it was excised completely. Two patients who had a lateral ventricle cyst located in the atrium but extending to quadrigeminal cyst were managed with 3 fenestrations. Two patients with a lateral ventricle arachnoid cyst located into the atrium of lateral ventricle and extending to the velum interpositum cistern through the choroid fissure were managed with 3 endoscopic fenestrations. Postoperatively, patients were followed clinically and by radiologic imaging. None of the patients reported recurrence until the latest follow-up.Multiple endoscopic fenestrations for lateral ventricle arachnoid cyst according to its location and anatomic extension help to reduce recurrence and good outcome. Cyst excision is recommended only when the cyst wall is easily separable from the lateral ventricle wall. Intraoperative use of thulium light amplification by stimulated emission of radiation helps in achieving early hemostasis and easy perforation of the thick cyst wall.

The insulin receptor (INSR) is an evolutionarily conserved signaling protein that regulates development and cellular metabolism. INSR signaling promotes neurogenesis in Drosophila; however, a specific role for the INSR in maintaining adult neural stem cells (NSCs) in mammals has not been investigated. We show that conditionally deleting the Insr gene in adult mouse NSCs reduces subventricular zone NSCs by ∼70% accompanied by a corresponding increase in progenitors. Insr deletion also produced hyposmia caused by aberrant olfactory bulb neurogenesis. Interestingly, hippocampal neurogenesis and hippocampal-dependent behaviors were unperturbed. Highly aggressive proneural and mesenchymal glioblastomas had high INSR/insulin-like growth factor (IGF) pathway gene expression, and isolated glioma stem cells had an aberrantly high ratio of INSR:IGF type 1 receptor. Moreover, INSR knockdown inhibited GBM tumorsphere growth. Altogether, these data demonstrate that the INSR is essential for a subset of normal NSCs, as well as for brain tumor stem cell self-renewal.

Background Obstructive hydrocephalus in adulthood can be caused by stenosis in the aqueductal area. Chronic changes lead to a dilatation of the lateral ventricles and ballooning of infratentorial recesses. In rare cases a rupture of the floor of the third ventricle (so-called spontaneous ventriculostomy) has been described in the literature. Case presentation: We present two cases of chronic obstructive hydrocephalus due to aqueductal stenosis in adult patients. Magnetic resonance imaging included phase-contrast-imaging and revealed significant flow through the floor of the third ventricle in keeping with spontaneous ventriculostomy. In addition to other typical changes associated with chronic hydrocephalus, a distinct flattening of the tectal plate could be identified in one case. Conclusion We present two cases of spontaneous ventriculostomy in patients with chronic hydrocephalus. To our knowledge, flattening of the tectal plate has not yet been described in the literature and may be caused by continuous cerebrospinal fluid-pulsation.

Background Glioblastoma is a treatment-resistant brain cancer. Its hierarchical cellular nature and its tumor microenvironment (TME) before, during, and after treatments remain unresolved. Methods Here, we used single-cell RNA sequencing to analyze new and recurrent glioblastoma and the nearby subventricular zone (SVZ). Results We found 4 glioblastoma neural lineages are present in new and recurrent glioblastoma with an enrichment of the cancer mesenchymal lineage, immune cells, and reactive astrocytes in early recurrences. Cancer lineages were hierarchically organized around cycling oligodendrocytic and astrocytic progenitors that are transcriptomically similar but distinct to SVZ neural stem cells (NSCs). Furthermore, NSCs from the SVZ of patients with glioblastoma harbored glioblastoma chromosomal anomalies. Lastly, mesenchymal cancer cells and TME reactive astrocytes shared similar gene signatures which were induced by radiotherapy in a myeloid-dependent fashion in vivo. Conclusion These data reveal the dynamic, immune-dependent nature of glioblastoma’s response to treatments and identify distant NSCs as likely cells of origin.

OBJECTIVE The tumor characteristics and surgical outcomes of intracranial subependymomas are poorly defined. In this study the authors aimed to provide a comprehensive review of all clinical, pathological, radiological, and surgical aspects of this important neoplasm to inform future management strategies. METHODS A systematic review and meta-analysis of MEDLINE, EMBASE, Cochrane, and Google Scholar databases adherent to PRISMA guidelines was conducted. RESULTS Of the 1145 articles initially retrieved, 24 studies encompassing 890 cases were included. The authors identified 3 retrospective cohort studies and 21 case series, but no controlled trials. Mean age at presentation was 46.7 ± 18.1 years with a male predominance (70.2%). Common sites of tumor origin were the lateral ventricle (44.5%) and fourth ventricle (43.1%). Cumulative postoperative mortality and morbidity rates were 3.4% and 24.3% respectively. Meta-analysis revealed that male sex (HR 3.15, 95% CI 1.39–7.14, p = 0.006) was associated with poorer 5-year overall mortality rates. All-cause mortality rates were similar when performing subgroup meta-analyses for age (HR 0.50, 95% CI 0.03–7.36, p = 0.61), smaller subependymoma size (HR 1.51, 95% CI 0.78–2.92, p = 0.22), gross-total resection (HR 0.65, 95% CI 0.35–1.23, p = 0.18), and receipt of postoperative radiation therapy (HR 0.88, 95% CI 0.27–2.88, p = 0.84). Postoperative Karnofsky Performance Index scores improved by a mean difference of 1.62 ± 12.14 points (p = 0.42). The pooled overall 5-year survival rate was 89.2%, while the cumulative recurrence rate was 1.3% over a median follow-up ranging from 15.3 to 120.0 months. The pure subependymoma histopathological subtype was most prevalent (85.6%), followed by the mixed subependymoma-ependymoma tumor variant (13.7%). CONCLUSIONS Surgical extirpation without postoperative radiotherapy results in excellent postoperative survival and functional outcomes in the treatment of intracranial subependymomas. Aggressive tumor behavior should prompt histological reevaluation for a mixed subependymoma-ependymoma subtype. Further high-quality controlled trials are still required to investigate this rare tumor.

In the adult ventricular-subventricular zone (V-SVZ), neural stem cells (NSCs) give rise to transit-amplifying progenitor (TAP) cells. These progenitors reside in different subniche locations, implying that cell movement must accompany lineage progression, but the dynamic behaviors of adult NSCs and TAPs remain largely unexplored. Here, we performed live time-lapse imaging with computer-based image analysis of young and aged 3D V-SVZ wholemounts from transgenic mice with fluorescently distinguished NSCs and TAP cells. Young V-SVZ progenitors are highly dynamic, with regular process outgrowth and retraction and cell migration. However, these activities dramatically declined with age. An examination of single-cell RNA sequencing (RNA-seq) data revealed age-associated changes in the Rho-Rock pathway that are important for cell motility. Applying a small molecule to inhibit ROCK transformed young into old V-SVZ progenitor cell dynamic behaviors. Hence RHO-ROCK signaling is critical for normal adult NSC and TAP movement and interactions, which are compromised with age, concomitant with the loss of regenerative ability.

The purpose of treatment for unilocular intracranial cysts (UICs) is to release elevated intracranial pressure. Neuroendoscopic fenestration (NF) is one of the most effective and minimally invasive options for treating UICs, especially in young children; however, the optimal location and number of fenestrations, the necessity of using endoscopic third ventriculostomy (ETV) in combination with fenestration, and the course of treatment are not well known. We retrospectively reviewed the hospital records between 2012 and 2019. The patients were studied in terms of sex, age at surgery, preoperative symptoms, cyst localization and size, course of treatment, ventricular diameter, developmental assessment, anatomical location, and the number of fenestrations. There were four eligible patients in the relevant period: two boys and two girls. The median age at the time of surgery was 16 months. With regard to the location of the cysts, there were two cases of cavum velum interpositum (CVI), one case of quadrigeminal cistern, and one case of an isolated lateral ventricle. The most common preoperative finding was an enlarged head circumference. All the patients were treated with NF, including one case of reoperation after open head surgery. Postoperatively, we used the frontal and occipital horn ratio (FOHR) to evaluate the ventricular size. The average reduction in the FOHR was 0.003. In the most recent developmental assessment or examination during the follow-up period, two patients showed normal development, and two patients showed developmental delay. Based on our past experience and reports, we believe that it is recommended to perform two fenestrations for a single cyst. This is because it creates a flow of cerebrospinal fluid (CSF) within the cyst into normal CSF reflux. For lesions with obstruction of the aqueduct, such as cysts in the quadrigeminal cistern, ETV should be considered if it can be performed safely, in preparation for the worsening of hydrocephalus due to obstruction by enlargement of the cyst.

Purpose The purpose of the present study was to evaluate contrast enhancement of the infundibular recess in the normal state using heavily T2-weighted 3D fluid-attenuated inversion recovery (FLAIR) (HT2-FLAIR). Methods Twenty-six patients were retrospectively recruited. We subjectively assessed overall contrast enhancement of the infundibular recess between postcontrast, 4-hour (4-h) delayed postcontrast, and precontrast HT2-FLAIR images. We also objectively conducted chronological and spatial comparisons by measuring the signal intensity (SI) ratio (SIR). Chronological comparisons were performed by comparing SI of the infundibular recess/SI of the midbrain (SIRIR-MB). Spatial comparisons were conducted by comparing SI on postcontrast HT2-FLAIR/SI on precontrast HT2-FLAIR (SIRPost-Pre) of the infundibular recess with that of other cerebrospinal fluid (CSF) spaces, including the superior part of the third ventricle, lateral ventricles, fourth ventricle, and interpeduncular cistern. Results In the subjective analysis, all cases showed contrast enhancement of the infundibular recess on both postcontrast and 4-h delayed postcontrast HT2-FLAIR, and showed weaker contrast enhancement of the infundibular recess on 4-h delayed postcontrast HT2-FLAIR than on postcontrast HT2-FLAIR. In the objective analysis, SIRIR-MB was the highest on postcontrast images, followed by 4-h delayed postcontrast images. SIRPost-Pre was significantly higher in the infundibular recess than in the other CSF spaces. Conclusion The present results demonstrated that the infundibular recess was enhanced on HT2-FLAIR after an intravenous gadolinium injection. The infundibular recess may be a potential source of the leakage of intravenously administered gadolinium into the CSF.

Neurogenesis in the adult brain takes place in two neurogenic niches: the ventricular-subventricular zone (V-SVZ) and the subgranular zone. After differentiation, neural precursor cells (neuroblasts) have to move to an adequate position, a process known as neuronal migration. Some studies show that in Alzheimer’s disease, the adult neurogenesis is impaired. Our main aim was to investigate some proteins involved both in the physiopathology of Alzheimer’s disease and in the neuronal migration process using the APP/PS1 Alzheimer’s mouse model. Progenitor migrating cells are accumulated in the V-SVZ of the APP/PS1 mice. Furthermore, we find an increase of Cdh1 levels and a decrease of Cdk5/p35 and cyclin B1, indicating that these cells have an alteration of the cell cycle, which triggers a senescence state. We find less cells in the rostral migratory stream and less mature neurons in the olfactory bulbs from APP/PS1 mice, leading to an impaired odour discriminatory ability compared with WT mice. Alzheimer’s disease mice present a deficit in cell migration from V-SVZ due to a senescent phenotype. Therefore, these results can contribute to a new approach of Alzheimer’s based on senolytic compounds or pro-neurogenic factors.

Made available in DSpace on 2022-04-29T08:36:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) This study aimed to perform quantitative and qualitative evaluations of the lateral and third ventricles, and brain parenchyma, in healthy dogs of different skull conformations on CT scans. Forty-five adult client-owned dogs were divided into three groups according to skull conformation: G1 (dolichocephalic)—15 German Shepherds; G2 (mesaticephalic)—15 Rottweilers; G3 (brachycephalic)—15 Boxers. Transverse plane images were used for quantitative and qualitative evaluations of the lateral ventricles and third ventricle, and pre- and post-contrast brain parenchyma. The height of both ventricles and brain was measured at the level of the interthalamic adhesion. Ventricle height, brain height, and ventricle/brain height ratio were statistically higher in G3 compared with G1 and G2 that were similar. The third ventricle was visible but unmeasurable in five dogs from G1 and three from G2. In G3, all dogs had third ventricle visible and measurable in all images. Asymmetric ventricles were seen in five dogs in Group 1 and Group 2, and seven in Group 3. Brain parenchyma had homogenous density in 80% of the dogs in all groups. Contrast enhancement of the rostral midline was visualized in all dogs. In conclusion, brain CT scans of healthy dogs showed that the qualitative data were similar among groups, but lateral ventricle and brain measurements in brachycephalic dogs differed from the dolichocephalic and mesaticephalic dogs. Department of Animal Reproduction and Veterinary Surgery School of Veterinary Medicine and Animal Science—São Paulo State University (UNESP) Department of Animal Reproduction and Veterinary Surgery School of Veterinary Medicine and Animal Science—São Paulo State University (UNESP) FAPESP: 09/06899-0

Infantile choroid plexus papilloma (CPP) associated with multiple peritumoral cysts is a rare variant of CPP, and clinical course and optimal management are largely unknown. A 9-month-old boy presented with a large solid tumor in the left lateral ventricle associated with multiple peritumoral cysts, arachnoid cysts, and hydrocephalus containing xanthochromic fluid with high protein content. Shrinkage of these cysts and resolution of hydrocephalus were achieved after total resection of the hypervascular solid part of the tumor. Histological examination confirmed the solid part of the tumor as CPP and showed that the wall of the peritumoral cysts consisted of reactive gliosis without neoplastic cells. Follow-up magnetic resonance imaging 12 months after surgery revealed that these cysts remained stable. CPP with nonenhancing peritumoral cysts can be managed by resection of only the solid part of the tumor without permanent cerebrospinal fluid diversion.

Hypoxia is involved in the regulation of various cell functions in the body, including the regulation of stem cells. The hypoxic microenvironment is indispensable from embryonic development to the regeneration and repair of adult cells. In addition to embryonic stem cells, which need to maintain their self‐renewal properties and pluripotency in a hypoxic environment, adult stem cells, including neural stem cells (NSCs), also exist in a hypoxic microenvironment. The subventricular zone (SVZ) and hippocampal dentate gyrus (DG) are the main sites of adult neurogenesis in the brain. Hypoxia can promote the proliferation, migration, and maturation of NSCs in these regions. Also, because most neurons in the brain are non‐regenerative, stem cell transplantation is considered as a promising strategy for treating central nervous system (CNS) diseases. Hypoxic treatment also increases the effectiveness of stem cell therapy. In this review, we firstly describe the role of hypoxia in different stem cells, such as embryonic stem cells, NSCs, and induced pluripotent stem cells, and discuss the role of hypoxia‐treated stem cells in CNS diseases treatment. Furthermore, we highlight the role and mechanisms of hypoxia in regulating adult neurogenesis in the SVZ and DG and adult proliferation of other cells in the CNS., Hypoxia promotes stem cell proliferation, differentiation, and survival. Hypoxia promotes the pluripotency, proliferation, and directed differentiation of embryonic stem cells (ESCs) and neural stem cells (NSCs) and helps induced pluripotent stem cells (iPSCs) to develop into different types of cells in vitro. Hypoxia is also involved in adult neurogenesis, angiogenesis, and gliogenesis. DG, dentate gyrus; LV, lateral ventricle; SVZ, subventricular zone.

Evidence on adult mammalian neurogenesis and scarce studies with human brains led to the idea that adult human neurogenesis occurs in the subgranular zone (SGZ) of the dentate gyrus and in the subventricular zone (SVZ). However, findings published from 2018 rekindled controversies on adult human SGZ neurogenesis. We systematically reviewed studies published during the first decade of characterization of adult human neurogenesis (1994–2004) – when the two-neurogenic-niche concept in humans was consolidated – and compared with further studies. The synthesis of both periods is that adult human neurogenesis occurs in an intensity ranging from practically zero to a level comparable to adult mammalian neurogenesis in general, which is the prevailing conclusion. Nonetheless, Bernier and colleagues showed in 2000 intriguing indications of adult human neurogenesis in a broad area including the limbic system. Likewise, we later showed evidence that limbic and hypothalamic structures surrounding the circumventricular organs form a continuous zone expressing neurogenesis markers encompassing the SGZ and SVZ. The conclusion is that publications from 2018 on adult human neurogenesis did not bring novel findings on location of neurogenic niches. Rather, we expect that the search of neurogenesis beyond the canonical adult mammalian neurogenic niches will confirm our indications that adult human neurogenesis is orchestrated in a broad brain area. We predict that this approach may, for example, clarify that human hippocampal neurogenesis occurs mostly in the CA1-subiculum zone and that the previously identified human rostral migratory stream arising from the SVZ is indeed the column of the fornix expressing neurogenesis markers.

Primary autosomal recessive microcephaly 5 (MCPH5) is a rare neurodevelopmental disorder with a relatively high incidence in regions where consanguineous marriage is widely practiced; So far, only a few MCPH5 cases have been reported from China. Here, we report clinical and molecular characteristics of two Chinese MCPH5 patients, a 24-year-old woman proband and her brother, a 19-year-old man, from a nonconsanguineous family. Main manifestations in the proband were small head circumference, premature closure of fontanelles, impaired concentration and moderate intellectual disability. The proband's brother had similar symptoms, but he was hyperactive and had a more severe sloping forehead. Brain imaging revealed global reduction in brain size, especially in the frontal lobes bilaterally and anterior horns of lateral ventricles. Sequencing results revealed that both patients carried a novel nonsense variant p.Tyr2004* (c.6012_6013delTA) and a novel frameshift variant p.Arg2005Serfs*48 (c.6015_6016delGG) in the ASPM gene. These variants were interpreted to be pathogenic in the in-silico analysis. Our findings help to expand the mutation spectrum of ASPM and provide new opportunities for assisting the traditional clinical diagnosis on the cases with atypical characteristics.

OBJECTIVE Neurodevelopmental delays and frontal lobe cortical dysmaturation are widespread among children with congenital heart disease (CHD). The subventricular zone (SVZ) is the largest pool of neural stem/progenitor cells in the postnatal brain. Our aim is to determine the effects of cardiopulmonary bypass (CPB) on neurogenesis and cortical maturation in piglets whose SVZ development is similar to human infants. METHODS Three-week-old piglets (n = 29) were randomly assigned to control (no surgery), mild-CPB (34°C full flow for 60 minutes) and severe-CPB groups (25°C circulatory-arrest for 60 minutes). The SVZ and frontal lobe were analyzed with immunohistochemistry 3 days and 4 weeks postoperatively. MRI of the frontal lobe was used to assess cortical development. RESULTS SVZ neurogenic activity was reduced up to 4 weeks after both mild and severe CPB-induced insults. CPB also induced decreased migration of young neurons to the frontal lobe, demonstrating that CPB impairs postnatal neurogenesis. MRI 4 weeks after CPB displayed a decrease in gyrification index and cortical volume of the frontal lobe. Cortical fractional anisotropy was increased after severe CPB injury, indicating a prolonged deleterious impact of CPB on cortical maturation. Both CPB-induced insults displayed a significant change in densities of three major inhibitory neurons, suggesting excitatory-inhibitory imbalance in the frontal cortex. In addition, different CPB insults altered different subpopulations of inhibitory neurons. INTERPRETATION Our results provide novel insights into cellular mechanisms contributing to CHD-induced neurological impairments. Further refinement of CPB hardware and techniques is necessary to improve long-term frontal cortical dysmaturation observed in children with CHD. ANN NEUROL 2021;90:913-926.

Human MYCN is an oncogene amplified in neuroblastoma and many other tumors. Both human MYCN and mouse Mycn genes are important in embryonic brain development, but their functions in adult healthy nerve system are completely unknown. Here, with Mycn-eGFP mice and quantitative RT-PCR, we found that Mycn was expressed in specific brain regions of young adult mice, including subventricular zone (SVZ), subgranular zone (SGZ), olfactory bulb (OB), subcallosal zone (SCZ), and corpus callosum (CC). With immunohistochemistry (IHC), we found that many Mycn-expressing cells expressed neuroblast marker doublecortin (DCX) and proliferation marker Ki67. With Dcx-creER and Mki67-creER mouse lines, we fate mapped Dcx-expressing neuroblasts and Mki67-expressing proliferation cells, along with deleting Mycn from these cells in adult mice. We found that knocking out Mycn from adult neuroblasts or proliferating cells significantly reduced cells in proliferation in SVZ, SGZ, OB, SCZ, and CC. We also demonstrated that the Mycn-deficient neuroblasts in SGZ matured quicker than wild-type neuroblasts, and that Mycn-deficient proliferating cells were more likely to survive in SVZ, SGZ, OB, SCZ, and CC compared to wild type. Thus, our results demonstrate that, in addition to causing tumors in the nervous system, oncogene Mycn has a crucial function in neurogenesis and oligodendrogenesis in adult healthy brain.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Prior studies examining the mutational landscape of GBM revealed recurrent alterations in genes that regulate the same growth control pathways. To this regard, ~ 40% of GBM harbor EGFR alterations, whereas BRAF variants are rare. Existing data suggests that gain-of-function mutations in these genes are mutually exclusive. This study was designed to explore the clinical, pathological, and molecular differences between EGFR- and BRAF-mutated GBM. We reviewed retrospective clinical data from 89 GBM patients referred for molecular testing between November 2012 and December 2015. Differences in tumor mutational profile, location, histology, and survival outcomes were compared in patients with EGFR- versus BRAF-mutated tumors, and microarray data from The Cancer Genome Atlas was used to assess differential gene expression between the groups. Individuals with BRAF-mutant tumors were typically younger and survived longer relative to those with EGFR-mutant tumors, even in the absence of targeted treatments. BRAF-mutant tumors lacked distinct histomorphology but exhibited unique localization in the brain, typically arising adjacent to the lateral ventricles. Compared to EGFR- and IDH1-mutant tumors, BRAF-mutant tumors showed increased expression of genes related to a trophoblast-like phenotype, specifically HLA-G and pregnancy specific glycoproteins, that have been implicated in invasion and immune evasion. Taken together, these observations suggest a distinct clinical presentation, brain location, and gene expression profile for BRAF-mutant tumors. Pending further study, this may prove useful in the stratification and management of GBM.

Traditionally, descriptions of germinal matrix hemorrhage (GMH), derived from observations in preterm and very preterm infants, indicate its location at the caudothalamic grooves. However, before the germinal matrix begins to recede at approximately 28 weeks’ gestational age (GA), it extends along the floor of the lateral ventricles far posterior to the caudothalamic grooves. Germinal matrix–intraventricular hemorrhage (GMH-IVH) can occur along any site from which the germinal matrix has not yet involuted. Therefore, as current advances in neonatology have allowed the routine survival of extremely preterm infants as young as 23 weeks’ GA, postnatal GMH-IVH can occur in previously undescribed locations. Hemorrhage in the more posterior GMH on head ultrasound, if unrecognized, may lead to errors in diagnosis and mislocalization of this injury to the periventricular white matter or lateral walls of the lateral ventricles instead of to the subependyma, where it is in fact located. Our aim is to describe posterior GMH in extremely premature infants, including its characteristic imaging appearance and potential pitfalls in diagnosis. Over a 5-year period, all consecutive extremely preterm infants of 27 weeks’ GA or less who developed GMH-IVH of any grade were included. A consecutive group of 100 very preterm infants of 31 weeks’ GA with a GMH-IVH of any grade served as controls. In 106 extremely preterm neonates (mean GA: 25 weeks, range: 23.1–26.6 weeks) with 212 potential lateral ventricular germinal matrix bleeding sites, 159 sites had bleeds. In 70/159 (44%), the GMH-IVH was located posterior to the caudothalamic grooves and the foramina of Monro, 52 (32.7%) were both anterior and posterior and 21 (13.2%) were exclusively anterior. In 16 ventricles with intraventricular hemorrhage, an origin site in the germinal matrix could not be determined. In the control population of very preterm infants, all hemorrhages were at the anterior caudothalamic grooves and 95% were grade I. Unlike the older very preterm and moderately preterm infants that form the basis of our GMH-IVH description and classification, the extremely preterm infants now routinely surviving have a more fetal pattern of germinal matrix distribution, which is reflected in a different distribution and size of germinal matrix injury. We report the postnatal occurrence of subependymal GMH-IVH in extremely preterm infants in these more primitive, posterior locations, its potential imaging pitfalls and sonographic findings.

Purpose: Non-aneurysmal perimesencephalic subarachnoid hemorrhage (PmSAH) represents 6.8% of spontaneous subarachnoid hemorrhage, and usually has a benign clinical course. However, patients might have early cerebral ischemic lesions and long-term neurocognitive complaints. Cerebral atrophy has been described in patients after aneurysmal SAH, but not in PmSAH. We aimed to investigate if PmSAH associates with increased brain volume loss. Methods: In this prospective study, we included consecutive patients with PmSAH that performed MR in the first 10 days after hemorrhage, and follow-up MR 6-7 years later. Automated volumetric measurements of intracranial, white matter, gray matter, whole brain, lateral ventricles, hippocampus, and amygdala volumes were performed. Volumes were compared to a normal population, matched for age. Results: Eight patients with PmSAH were included, with a mean age of 51.5 (SE 3.6) at baseline. The control group included 22 patients with a mean age of 56.3 (SE 2.0). A relative reduction of all volumes was found in both groups; however, PmSAH patients had significant reductions in intracranial, white and gray matter, whole brain, and hippocampal volumes when compared to controls. These changes had a higher magnitude in whole brain volume, with a significant absolute decrease of 6.5% in PmSAH patients (versus 1.9% in controls), and a trend for an increase in lateral ventricle volume (absolute 21.3% increase, versus 3.9% in controls). Conclusion: Our cohort of PmSAH patients showed significant long-term parenchymal atrophy, and higher global and focal parenchymal volume loss rates when compared to a non-SAH population. info:eu-repo/semantics/publishedVersion

BACKGROUND: Magnetic resonance imaging (MRI) has become important in the diagnostic work-up of neurodegenerative diseases. icobrain dm, a CE-labeled and FDA-cleared automated brain volumetry software, has shown potential in differentiating cognitively healthy controls (HC) from Alzheimer's disease (AD) dementia (ADD) patients in selected research cohorts. OBJECTIVE: This study examines the diagnostic value of icobrain dm for AD in routine clinical practice, including a comparison to the widely used FreeSurfer software, and investigates if combined brain volumes contribute to establish an AD diagnosis. METHODS: The study population included HC (n = 90), subjective cognitive decline (SCD, n = 93), mild cognitive impairment (MCI, n = 357), and ADD (n = 280) patients. Through automated volumetric analyses of global, cortical, and subcortical brain structures on clinical brain MRI T1w (n = 820) images from a retrospective, multi-center study (REMEMBER), icobrain dm's (v.4.4.0) ability to differentiate disease stages via ROC analysis was compared to FreeSurfer (v.6.0). Stepwise backward regression models were constructed to investigate if combined brain volumes can differentiate between AD stages. RESULTS: icobrain dm outperformed FreeSurfer in processing time (15-30 min versus 9-32 h), robustness (0 versus 67 failures), and diagnostic performance for whole brain, hippocampal volumes, and lateral ventricles between HC and ADD patients. Stepwise backward regression showed improved diagnostic accuracy for pairwise group differentiations, with highest performance obtained for distinguishing HC from ADD (AUC = 0.914; Specificity 83.0%; Sensitivity 86.3%). CONCLUSION: Automated volumetry has a diagnostic value for ADD diagnosis in routine clinical practice. Our findings indicate that combined brain volumes improve diagnostic accuracy, using real-world imaging data from a clinical setting. ispartof: JOURNAL OF ALZHEIMERS DISEASE vol:83 issue:2 pages:623-639 ispartof: location:Netherlands status: published

Pyruvate carboxylase (PC) deficiency (MIM# 266150) is an autosomal recessive disorder with three subtypes. Patients homozygous for the c.1828G > A mutation in the PC gene belong to type A, which typically has infantile onset, severe to profound developmental delay, hypotonia, and lactic acidemia. We report the neuroimaging abnormalities in a 33‐week gestation infant homozygous for the c.1828G > A mutation. Brain magnetic resonance imaging on day 10 of life revealed increased T2 signal within the subcortical and periventricular white matter, an immature gyral pattern, large periventricular cysts with mass effect on the lateral ventricles, and dilatation of the occipital and temporal horns. Magnetic resonance spectroscopy showed reduced creatine and NAA peaks, a relatively high choline peak and no lactate peak. These findings were observed prior to the neonate experiencing any episodes of decompensation with lactic acidosis. The presence of these brain anomalies at this gestational age, prior to any metabolic decompensation, supports the essential role of PC in normal brain morphogenesis and the resulting in‐utero brain anomalies secondary to its deficiency. Our experience with this affected premature infant and many others we have managed with the same founder mutation suggests that the clinical phenotypes of the type A and the more severe type B PC deficient patients are on a spectrum rather than distinct subtypes.

Целью данной работы является изучение межполушарной асимметрии и гендерных различий морфометрических параметров отдельных частей боковых желудочков головного мозга. В процессе исследования был проведен анализ томограмм 120 детей трех лет, из которых 60 – лиц мужского пола, 60 – женского пола. Для исследования были использованы архивные данные размеров частей боковых желудочков, полученные методом магнитно-резонансной томографии. Результатом исследования явилось определение межполушарной асимметрии боковых желудочков: центральная часть левого желудочка у мальчиков на 6,4% превосходила таковую справа; нижний рог левого бокового желудочка у мальчиков был меньше правого на 6,3%; у девочек ширина центральная части левого бокового желудочка превосходила таковую справа на 10,5%. Помимо этого, были установлены половые особенности морфометрических характеристик боковых желудочков: длина нижнего рога левого бокового желудочка у девочек на 4,3% превосходит таковую у мальчиков., The aim of this work is to study interhemispheric asymmetry and gender differences in morphometric parameters of separate parts of the lateral ventricles of the brain. The research involved the analysis of tomograms of 120 three-year-old children, of whom 60 were males and 60 were females. Archived data on the size of the parts of the lateral ventricles obtained by magnetic resonance imaging were used for the study. The result of the study was the determination of interhemispheric asymmetry of the lateral ventricles: the central part of the left ventricle in boys was 6.4% greater than that in the right; the lower horn of the left lateral ventricle in boys was 6.3% smaller than that in the right; in girls, the central width of the left lateral ventricle was 10.5% greater than that in the right. In addition, there were gender-specific morphometric characteristics of the lateral ventricles: the length of the lower horn of the left lateral ventricle in girls was 4.3% greater than in boys., Международный научно-исследовательский журнал, Выпуск 11 (125) 2022

Neural stem cells (NSCs) are self-renewing, multipotent cells which give rise to all components of the central nervous system (CNS) during embryogenesis, but also activate in response to injury and disease and maintain a certain level of neurogenic activity throughout adulthood. This activity takes place in specialized regions of the brain, the neurovascular niches, whose main role is to control the behaviour of the CNS. In adult mammals, two main "canonical" niches have been described: The subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus. This review discusses our current understanding of the neural stem cells and their canonical niches, as well as their structure, behaviours, and role in neural disease. This research was funded by the Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III grants PI18/00462 to M.V.G.-G. and PT20/00044 to M.D., was cofinanced by the European Regional Development Fund, “A way of making Europe” initiative. This work was partially supported by Comunidad de Madrid (S2017/BMD-3867 RENIM-CM) and cofinanced by the European Structural and Investment Fund. This study was also supported by the Plan Estatal de I+D+I 2013–2016, with funding from the European Regional Development Fund (ERDF), “A way to build Europe” initiative. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation and is a Severo Ochoa Centre of Excellence (SEV-2015-0505). Sí

We report an autopsy case of Fahr's syndrome in an 85-year-old woman associated with asymptomatic hypoparathyroidism. The patient was diagnosed as having brain calcification at 65 years of age. She developed mild dementia at 75, parkinsonism at 76, and severe dementia at 82. Computed tomography revealed extensive, symmetric intracranial calcification, involving both sides of the basal ganglia and cerebellar dentate nuclei, and severe cerebral atrophy that developed afterwards. A neuropathological examination revealed intracranial calcification, particularly in the wall of the arterioles and capillaries having numerous calcium deposits. Severe vascular calcification and severe neuronal loss without α-synuclein accumulation were found in the substantia nigra. There were high-level neuropathological changes indicative of Alzheimer's disease. Although the colocalization of calcium and amyloid-β deposits in the same arterial wall was rare, both of them were located in a similar layer of the arterial wall. The vascular calcification in the basal ganglia spread continuously through the corona radiata into the selective cerebral areas along the medullary arteries, but did not involve the corpus callosum or insular region. Stone formation was observed at the corona radiata adjacent to the superolateral angles of the lateral ventricles. We hypothesized that there would be a stereotypical extension pattern of vascular calcification related to the arrangement of penetrating arteries in Fahr's syndrome.

Abnormal migration of subventricular zone (SVZ)-derived neural progenitor cells (SDNPs) is involved in the pathological and epileptic processes of focal cortical dysplasias (FCDs), but the underlying mechanisms are not clear. Recent studies indicated that high mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) are widely expressed in epileptic specimens of FCDs, which suggests that the HMGB1-RAGE pathway is involved in the pathological and/or epileptic processes of FCDs. The present study used Nestin-GFPtg/+ transgenic mice, and we established a model of freezing lesion (FL), as described in our previous report. A "migrating stream" composed of GFP-Nestin+ SDNPs was derived from the SVZ region and migrated to the cortical FL area. We found that translocated HMGB1 and RAGE were expressed in cortical lesion in a clustered distribution pattern, which was especially obvious in the early stage of FL compared to the sham group. Notably, the number of GFP-Nestin+ SDNPs within the "migrating stream" was significantly decreased when the HMGB1-RAGE pathway was blocked by a RAGE antagonist or deletion of the RAGE gene. The absence of RAGE also decreased the activity of pentylenetetrazol-induced cortical epileptiform discharge. In summary, this study provided experimental evidence that the levels of extranuclear HMGB1 and its receptor RAGE were increased in cortical lesion in the early stage of the FL model. Activation of the HMGB1-RAGE pathway may contribute to the abnormal migration of SDNPs and the hyperexcitability of cortical lesion in the FL model.

The primary anatomical defect leading to periventricular nodular heterotopia occurs within the neural progenitors along the neuroepithelial lining of the lateral ventricles and results from a defect in the initiation of neuronal migration, following disruption of the neuroependyma and impaired neuronal motility. Growing evidence indicates that the FLNA-dependent actin dynamics and regulation of vesicle formation and trafficking by activation of ADP-ribosylation factors (ARFs) can play an important role in this cortical malformation. We report the first inherited variant of ARF1 in a girl with intellectual disability and periventricular nodular heterotopia who inherited the variant from the father with previously undiagnosed single nodular heterotopia and mild clinical expression. Additionally, both patients presented some features suggestive of hypohidrotic ectodermal dysplasia. These clinical features showed similarities to those of three previously reported cases with ARF1 missense variants, confirming that haploinsufficiency of this gene causes a recognisable neurological disorder with abnormal neuronal migration and variable clinical expressivity.

Background Large intraventricular tumors (IVTs) impose technical and surgical challenges, due to their enormous sizes, mass effect, vast extensions, and vascularity. Objective The authors aim at presenting their results, clinical outcomes, and the surgical strategies in the management of large IVTs through transcortical approaches. Methods A prospective trial was conducted at the Main Hospital of Alexandria University, Egypt, between August 2018 and October 2020 on 20 patients harboring IVTs larger than 5 cm or bilaterally represented. The variables evaluated included the extent of resection, postoperative neurological deficits, blood loss, surgical approaches, intraoperative challenges, complications, adjuvant therapies, Glasgow Outcome Scale, hydrocephalus, and cerebrospinal fluid (CSF) diversion. Results The study included 20 cases (9 males and 11 females). Mean age at diagnosis was 16.1 years (range 1–45). Mean follow-up was 12 months (range 9–26). Primary tumor locations were ventricular body, atrium, temporal horn, and frontal horn in 11, 5, 3, and 1 cases, respectively. Main pathologies were central neurocytomas (7 patients/35%), ependymomas (3 patients/15%), and subependymal giant cell astrocytoma (SEGA) (3 patients/15%). Excision was gross total (n = 19) and near-total (n = 1). Significant intraoperative bleeding (n = 6). Postoperative minor intraventricular hemorrhage (n = 6), subdural collections (n = 8), hydrocephalus (n = 9), memory affection (n = 4), and motor deficits (n = 4). Postoperative Glasgow Outcome Scale of 5/5 (n = 20), no mortalities were recorded. preoperative seizures (n = 7), new onset postoperative seizures (n = 2). Conclusion Surgical approaches to large tumors of the lateral ventricles should be tailored to the variability of tumor locations, dimensions, extensions, and the individual morbid anatomy, in addition to the surgeon’s experience and preferences. Trans-cortical approaches can provide safe surgical corridors to tackle these challenging subtypes of IVTs with good clinical outcomes, tumor resectability rates, and seizure control.

It has been commonly accepted for a long time that the cerebrospinal fluid (CSF) drains into arachnoid granulations from the subarachnoid space to the dural venous sinus unidirectionally. However, recently, periventricular capillaries and lymphatic concepts have been introduced. The CSF moves along the perivascular space and drains into the capillary vessels or meningeal lymphatic tissues. CSF is involved in removing brain waste out of the brain. In this study, we investigated the outflow mechanism of substances in the CSF from the brain. We investigated the movement of CSF by injection of gold colloid conjugates (2, 40, and 200 nm) into the lateral ventricles of mouse fetuses and evaluated the deposition by silver stain with tissue transparency and electron microcopy. Cadaverine was also injected into the lateral ventricle to determine its movement tract. The gold particle deposition was mainly observed in the frontal skull base. Electron microscopic study showed that the gold particle deposition was observed on the choroid plexus and ependyma in the lateral ventricle and also red blood cells in the heart and liver. Two-nanometer particles were exclusively observed in the liver. Cadaverine injection study demonstrated that cadaverine was observed at the extracranial frontal skull base, choroid plexus, ependymal surface, and perivascular area in the brain white matter. The particles in the CSF were shown to move from the brain to the frontal skull base and also into the blood stream through the choroid plexus in the fetus. The outflow of particles in the CSF may be regulated by molecular size. This new information will contribute to the prevention of brain degeneration due to brain waste deposition.

Seizures are common neurological emergencies that occasionally cause prolonged impairment of consciousness. The aim of this retrospective single-center study is to clarify factors associated with prolonged impairment of consciousness for admitted adult patients investigating patient backgrounds, blood tests, electroencephalographic patterns, and MRI findings. The patients who were admitted to the hospital due to epileptic seizures were classified into two groups: (1) early recovery group, in which patients recovered their consciousness within 6 hr, and (2) delayed recovery group, in which patients showed impairment of consciousness more than 6 hr. Factors associated with prolonged impairment of consciousness were compared between these groups. In this study, 42 cases (33 patients), with a mean age of 67.8 years, were included. Fifteen cases (13 patients) and 27 cases (20 patients) were classified into the early and delayed recovery groups, respectively. The populations of older patients and patients from a nursing home were significantly higher in the delayed recovery group. With regard to radiological analyses, a high grade of periventricular hyperintensity (PVH), high Evans index score, and enlarged bilateral atrial widths were significantly associated with prolonged impairment of consciousness. Multivariable analyses showed that a high grade of PVH was significantly associated with delayed recovery of consciousness independent of age and status epilepticus. In conclusion, we proposed that diffuse white matter degeneration around the lateral ventricles contributes to prolonged impairment of consciousness.

The periventricular and deep white matter of the immature brain of premature infants has an increased vulnerability to various, primarily ischemic injuries. The leading mechanism of selective vulnerability of the white matter of the large hemispheres in children with a low gestation period is the lack of formation of adjacent blood circulation zones between the main arteries of the developing brain. Magnetic resonance imaging has a high sensitivity to detect damage to the brain substance, both in the acute period and in the period of long-term outcomes. Periventricular leukomalacia (PVL) is one of the variants of brain damage in premature infants and the most common term in the conclusions of diagnostic doctors (ultrasound, CT, MRI). Considering the pathomorphological criteria, not always detected changes in the white matter of the large hemispheres are PVL. Diffuse (telencephalic) gliosis and diffuse leukomalacia are ordinary and typical variants of damage to the white matter of the large hemispheres in extremely premature infants, with a gestation period of up to 30-32 weeks. In the first variant, atrophic changes predominate with a pronounced decrease in the volume of white matter and a secondary expansion of the lateral ventricles. Diffuse leukomalacia is most often mistaken for PVL, but the localization of the white matter lesion of the large hemispheres is extensive and extends beyond the peri- and paraventricular region. Clinical examples show various variants of primary non-hemorrhagic brain lesions in prematurely born children in the long-term period. The analysis of the revealed changes is carried out, taking into account current data on developing the brain and pathomorphological criteria.

Myelin damage and abnormal remyelination processes lead to central nervous system dysfunction. Glial activation-induced microenvironment changes are characteristic features of the diseases with myelin abnormalities. We previously showed that ginsenoside Rg1, a main component of ginseng, ameliorated MPTP-mediated myelin damage in mice, but the underlying mechanisms are unclear. In this study we investigated the effects of Rg1 and mechanisms in cuprizone (CPZ)-induced demyelination mouse model. Mice were treated with CPZ solution (300 mg· kg(−1)· d(−1), ig) for 5 weeks; from week 2, the mice received Rg1 (5, 10, and 20 mg· kg(−1)· d(−1), ig) for 4 weeks. We showed that Rg1 administration dose-dependently alleviated bradykinesia and improved CPZ-disrupted motor coordination ability in CPZ-treated mice. Furthermore, Rg1 administration significantly decreased demyelination and axonal injury in pathological assays. We further revealed that the neuroprotective effects of Rg1 were associated with inhibiting CXCL10-mediated modulation of glial response, which was mediated by NF-κB nuclear translocation and CXCL10 promoter activation. In microglial cell line BV-2, we demonstrated that the effects of Rg1 on pro-inflammatory and migratory phenotypes of microglia were related to CXCL10, while Rg1-induced phagocytosis of microglia was not directly related to CXCL10. In CPZ-induced demyelination mouse model, injection of AAV-CXCL10 shRNA into mouse lateral ventricles 3 weeks prior CPZ treatment occluded the beneficial effects of Rg1 administration in behavioral and pathological assays. In conclusion, CXCL10 mediates the protective role of Rg1 in CPZ-induced demyelination mouse model. This study provides new insight into potential disease-modifying therapies for myelin abnormalities.

PURPOSE In this study, a simulator for training lateral ventricular puncture (LVP) was developed using three-dimensional (3D) printing technology, and its function of improving the skills of LVP in young interns was evaluated. METHODS A virtual 3D craniocerebral simulator of a 51-year-old female patient with hydrocephalus was reconstructed with 3D printing technology. The anatomical and practical validity were assessed by all interns on a 13-item Likert scale. The usefulness of this simulator was evaluated once a week by two neurosurgeons, based on the performance of the interns, using the objective structured assessment of technical skills (OSATS) scale. RESULTS The Likert scale showed that all participants agreed with the overall appearance of the simulator. Also, the authenticity of the skull was the best, followed by the lateral ventricles, analog generation system of intraventricular pressure, cerebrum, and the scalp. This simulator could help the participants' learning about the anatomy of the lateral ventricle, effective training, and repeating the steps of LVP. During training, the interns' ratio of success in LVP elevated gradually. At each evaluation stage, all mean performance scores for each measure based on the OSATS scale were higher than the previous. CONCLUSIONS The 3D printed simulator for LVP training provided both anatomical and practical validity, and enabled young doctors to master the LVP procedures and skills.

Background Absence of the cavum septum pellucidum (CSP) can be associated with a wide spectrum of congenital brain malformations. It is necessary to describe the anatomic structures that can be mistaken for the CSP in cases of septal agenesis. Results We retrospectively studied MRI of 12 fetuses referred with suspicion of absent CSP on sonography. The structures simulating CSP in axial sections (Pseudo septum) are: volume averaging from the medial edge of the frontal lobes (lateral ventricles) in the anterior aspect, fornices in the mid and posterior aspect and internal cerebral veins in the postero-inferior aspect. Eleven out of the twelve suspected cases of absent CSP showed a false positive ‘pseudo-septum’ appearance in axial sections of fetal brain MRI. The absence of the ‘pseudo-septum’ was confirmed on coronal MRI sections of the fetal brain. Conclusion It is important to study the axial and coronal sections of the fetal brain for accurate diagnosis of septal agenesis.

Adult neurogenesis is the production of new nerve cells in the adult brain. Neurogenesis is a clear example of the neuroplasticity phenomenon which can be observed in most of mammalian species, including human beings. This phenomenon occurs, at least, in two regions of the brain: the subgranular zone of the dentate gyrus in hippocampus and the ventricular zone of lateral ventricles. Numerous studies have investigated the relationship between sex steroid hormones and neurogenesis of adult brain; of which, mostly concentrated on the role of estradiol. It has been shown that estrogen plays a significant role in this process through both classic and non-classic mechanisms, including a variety of different growth factors. Therefore, the objective of this review is to investigate the role of female sex steroids with an emphasis on estradiol and also its potential implications for regulating the neurogenesis in the adult brain.

This article belongs to the Special Issue Frontiers in Neurogenesis—Series II Neural stem cells (NSCs) are self-renewing, multipotent cells which give rise to all components of the central nervous system (CNS) during embryogenesis, but also activate in response to injury and disease and maintain a certain level of neurogenic activity throughout adulthood. This activity takes place in specialized regions of the brain, the neurovascular niches, whose main role is to control the behaviour of the CNS. In adult mammals, two main 'canonical' niches have been described: The subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus. This review discusses our current understanding of the neural stem cells and their canonical niches, as well as their structure, behaviours, and role in neural disease. This research was funded by the Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III grants PI18/00462 to M.V.G.-G. and PT20/00044 to M.D., was co-financed by the European Regional Development Fund, "A way of making Europe" initiative. This work was partially supported by Comunidad de Madrid (S2017/BMD-3867 RENIM-CM) and co-financed by the European Structural and Investment Fund. This study was also supported by the Plan Estatal de I+D+I 2013-2016, with funding from the European Regional Development Fund (ERDF), "A way to build Europe" initiative. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation and is a Severo Ochoa Centre of Excellence (SEV-2015-0505)

Nuclear factor one X (NFIX) is a transcription factor required for normal ependymal development. Constitutive loss of

Accurate diagnosis of Alzheimer's disease (AD) in early stage can control the disease progression. Enlargement of Lateral Ventricles (LV) is one of the significant imaging biomarkers for the differentiation of Alzheimer's conditions. However, segmentation of accurate LV for analysis is still challenging. In this work, an attempt is made to segment LV regions from brain MR images using the UNet++ model. For this, axial scans of the MR images are taken from the publicly available Open Access Series of Imaging Studies (OASIS) Brain dataset. LV-based region of interest is segmented using the UNet++ network. Results show that the proposed approach is able to segment brain regions in Alzheimer's conditions. The UNet++ network model yields the highest dice score of 99.4% and sensitivity of 99.3% in segmenting the LV brain region. Thus, the proposed method could be useful for characterizing Alzheimer's condition.

The generation of new neurons in the adult brain throughout life is integral to brain plasticity and repair. Adult neural stem cells (aNSCs), present in the subventricular zone (SVZ) of the lateral ventricle wall and the subgranular zone (SGZ) of the hippocampal dentate gyrus, divide symmetrically or asymmetrically to maintain the stem cell pool or become committed progenitors and differentiate into various cell lineages. Depletion or dysregulation of aNSCs impairs proper brain connectivity and function and can contribute to several brain diseases including cognitive and neurodegenerative disorders and brain cancer. In this chapter, we present our optimized method to obtain and maintain reproducible neurosphere cultures from the adult mouse brain followed by evaluation of self-renewal using the extreme limiting dilution assay (ELDA) software. We use this assay routinely on aNSCs obtained from patient mouse models to generate log fraction plots and provide confidence intervals for all limiting dilution assay (LDA) data. At the same time, given the low number of NSCs required for the completion of the ELDA experiment, it is feasible to employ this approach to conduct high-content compound screening for therapeutic interventions aimed at enhancing the stem cell pool or combating a cohort of genetic and epigenetic disorders.

Neurogenesis is a biological process characterized by new neurons formation from stem cells. For decades, it was believed that neurons only multiplied during development and in the postnatal period but the discovery of neural stem cells (NSCs) in mature brain promoted a revolution in neuroscience field. In mammals, neurogenesis consists of migration, differentiation, maturation, as well as functional integration of newborn cells into the pre-existing neuronal circuit. Actually, NSC density drops significantly after the first stages of development, however in specific places in the brain, called neurogenic niches, some of these cells retain their ability to generate new neurons and glial cells in adulthood. The subgranular (SGZ), and the subventricular zones (SVZ) are examples of regions where the neurogenesis process occurs in the mature brain. There, the potential of NSCs to produce new neurons has been explored by new advanced methodologies and in neuroscience for the treatment of brain damage and/or degeneration. Based on that, this review highlights endogenous factors and drugs capable of stimulating neurogenesis, as well as the perspectives for the use of NSCs for neurological and neurodegenerative diseases.

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease, and its incidence is predicted to increase worldwide. Striatal dopamine depletion caused by substantia nigra (SN) degeneration is a pathological hallmark of PD and is strongly associated with cardinal motor and non-motor symptoms. Previous studies have reported that exercise increases neuroplasticity and promotes neurorestoration by increasing neurotrophic factors and synaptic strength and stimulating neurogenesis in PD. In the present study, we found that rotarod walking exercise, a modality of motor skill learning training, improved locomotor disturbances and reduced nigrostriatal degeneration in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In addition, our exercise regimen improved MPTP-induced perturbation of adult neurogenesis in some areas of the brain, including the subventricular zone, subgranular zone, SN, and striatum. Moreover, rotarod walking activated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and induced brain-derived neurotrophic factor (BDNF) expression in these regions. The results suggest that motor skill learning training using rotarod walking improves adult neurogenesis and restores motor performance by modulating the AMPK/BDNF pathway. Therefore, our findings provide evidence for neuroprotective effects and improved neuroplasticity in PD through motor skill learning training.

An entrapped temporal horn (ETH) is one of the critical complications after tumor removal in the lateral ventricle trigone that sometimes becomes life threatening.We sought to develop a novel intraoperative method of prophylactic intraventricular piping (PIP) just after tumor removal to prevent ETH.Three patients with meningiomas in the lateral ventricle trigone were treated by a novel intraoperative method of PIP just after tumor removal to prevent ETH. Silicone catheters normally used as ventricular drainage catheters were cut to 5- to 6-cm length and inserted into the tumor cavity to ensure communication between the temporal horn and the atrium or the body of the lateral ventricle through the piping straddling the trigone.None of our patients developed ETH during the follow-up period without complications caused by the tube placement.PIP might be beneficial to prevent ETH because constant osmotic pressure and constant cerebrospinal fluid pulse wave transmission are maintained between each compartment of the lateral ventricle.

As the largest concentrated region of neural stem cells in the adult brain, the subventricular zone (SVZ) is considered to have a close relationship with the origin of gliomas. An in-depth study of the characteristic manifestations associated with SVZ involvement in glioma may provide new ideas for individualized diagnosis and treatment of this fatal disease.All 279 patients with glioma who underwent surgical treatment in our department from January 2016 to December 2021 were included. Clinical and imaging data were collected, and telephonic follow-up was conducted to analyze the overall survival and progression-free survival. Prognostic factors including SVZ involvement on glioblastoma patients' survival were analyzed. Next, the relationship between SVZ involvement, a set of unique imaging features and gene status were determined respectively. The chi-squared test, logistics regression, and Cox regression were used for statistical analysis.The patients were divided into the SVZ involvement group (n = 198, 70.97 %) and SVZ non-involvement group (n = 81, 29.03 %). The median overall survival and progression-free survival were 13 months and 7 months for the SVZ involvement group, but 25 months and 17 months for the SVZ non-involvement group, respectively. In multivariate Cox survival analysis, MRI SVZ involvement proved an independent risk factor for the survival of patients with glioblastoma. The patients with SVZ involvement sign had a lower rate of cystic lesion (32.32 % vs. 48.48 %, p = 0.029), and a larger mean maximum diameter (5.88 ± 1.28 vs. 3.28 ± 1.65 cm). Compared with high grade gliomas (HGG), T1 enhancement (25.25 % vs. 10.42 %, p = 0.041) and homogeneous signal on T2WI (14.14 % vs. 43.75 %, p = 0.025) were independently associated with SVZ involvement in WHO grade 2 gliomas(LGG). In the gene status analysis, the SVZ involvement group showed the lower rate of MGMT promoter methylation (57.58 % vs. 79.17 %, p = 0.017).SVZ involvement in MRI at diagnosis is an independent negative prognostic indicator for the survival of glioblastoma patients. Some image signs are associated with SVZ involvement in HGG and LGG respectively. The unique imaging and gene features of gliomas with SVZ involvement indicate that this kind of tumor maybe a unique subgroup of gliomas.

AIM: This study aimed to describe and analyze the advantages and disadvantages of various surgical approaches to neoplasms of the third ventricle of the brain in children. MATERIALS AND METHODS: This study analyzed surgical interventions to the third ventricle in 657 patients, performed at the Academician N.N. Burdenko of the Research Institute of Neurosurgery from 1998 to 2018. These included 375 patients with intra-extraventricular craniopharyngiomas and 282 patients with gliomas of the third ventricle and chiasm. The patients age ranged from 3 mon to 18 years old. RESULTS: The anterior transcallosal approach provides access to the anterior horn and bodies of the lateral ventricles, as well as the third ventricle. The transfornical approach provides more opportunities for access to both the anterior and posterior parts of the third ventricle; however, it has a high risk of trauma to the fornix. The subchoroidal approach provides a very good view of the posterior parts of the third ventricle, especially of the pineal region; however, it has even greater restrictions on viewing its anterior parts. When compared with the transcallosal approach, the transfrontal approach can be used more safely in the absence of hydrocephalus (if the tumor is located in the anterior horn). No specific complications were inherent in a particular approach (seizures were registered in 1%, transient hemiparesis was noted in 10%, and transient memory impairments were revealed in 5% of cases). CONCLUSION: The use of a transcallosal approach is safe even in infants. The transcortical approach is recommended mainly for large tumors of the lateral ventricles, and the transcallosal approach should be used for small tumors of the third ventricle. No specific complications were inherent in a particular approach, and the choice was determined by the assessment of the exact location of the tumor and calculation of the most relevant trajectory for its achievement as well as the aim (biopsy or radical removal). Analysis of magnetic resonance imaging and neuronavigation are significant in the selection of surgical approaches.

BACKGROUND The distribution and growth of cells on nanofibrous scaffolds seem to be an indispensable precondition in cell tissue engineering. The potential use of biomaterial scaffolds in neural stem cell therapy is increasingly attracting attention. AIM In this study, we produced porous nanofibrous scaffolds fabricated from random poly-L-lactic acid (PLLA) to support neurogenic differentiation of neural stem and progenitor cells (NSPCs), isolated from the subventricular zone (SVZ) of the adult mouse brain. METHODS The viability and proliferation of the NSPCs on the nanofibrous PLLA scaffold were also tested by nuclear staining with 4, 6-diamidino-2-phenylindole dihydrochloride (DAPI), 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and scanning electron microscopy (SEM). To investigate the differentiation potential of NSPCs on the scaffolds, the cells were treated with a neurogenic differentiation medium, and immunostaining was done to detect neuronal and glial cells after 14 and 21 days of cultivation. Furthermore, the morphology of differentiated cells on the scaffold was examined using SEM. RESULTS The DAPI staining revealed the proliferation of NSPCs onto the surface of the nanofibrous PLLA scaffold. DAPI-positive cells were counted on days 2 and 5 after cultivation. The mean number of cells in each microscopic field was significantly (p