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After a stroke, the neurogenic response from the subventricular zone (SVZ) to repair the brain is limited. Microglia, as an integral part of the distinctive SVZ microenvironment, control neural stem / precursor cell (NSPC) behavior. Here, we show that discrete stroke-associated SVZ microglial clusters negatively impact the innate neurogenic response, and we propose a repository of relevant microglia-NSPC ligand-receptor pairs. After photothrombosis, a mouse model of ischemic stroke, the altered SVZ niche environment leads to immediate activation of microglia in the niche and an abnormal neurogenic response, with cell-cycle arrest of neural stem cells and neuroblast cell death. Pharmacological restoration of the niche environment increases the SVZ-derived neurogenic repair and microglial depletion increases the formation and survival of newborn neuroblasts in the SVZ. Therefore, we propose that altered cross-communication between microglial subclusters and NSPCs regulates the extent of the innate neurogenic repair response in the SVZ after stroke., (© 2024. The Author(s).)

Aneurysms of the anterior choroidal artery (AChA) are the most common pathology of the vessel. Although proximal aneurysms at the internal carotid artery (ICA) and AChA junction are common, their occurrence in the distal segment of the AChA is quite rare. We report a case of a distal AChA aneurysm occurring in the intraplexal segment of the AChA. To our knowledge, this is the first reported case of an intraplexal distal AChA aneurysm., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Intraventricular schwannomas are extremely rare, typically benign tumors originating from Schwann cells, which are not normally found within the ventricular system. Their presence challenges conventional understanding of tumor origins and complicates diagnosis and management. We report the case of a 19-year-old female presenting with a drop attack and headache, with no significant medical history. MRI revealed a heterogeneously enhancing lesion in the right lateral ventricle. Differential diagnoses included malignant tumors; however, histopathological examination post-surgical resection confirmed an intraventricular schwannoma. Postoperative outcomes were favorable, with successful CSF diversion via a right occipital ventriculoperitoneal shunt for isolated right temporal hydrocephalus. This case is notable for its atypical presentation in a young patient, challenging the conventional understanding that intraventricular schwannomas primarily affect older individuals. In addition, the correct diagnosis and successful management of a rare intraventricular schwannoma underscores the importance of considering this rare diagnosis in patients with nonspecific neurological symptoms and intraventricular lesions. This case, alongside the literature review, enriches the body of evidence on intraventricular schwannomas, highlighting the critical role of surgical intervention and the need for a comprehensive diagnostic approach., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Brain injury is highly associated with preterm birth. Complications of prematurity, including spontaneous or necrotizing enterocolitis (NEC)-associated intestinal perforations, are linked to lifelong neurologic impairment, yet the mechanisms are poorly understood. Early diagnosis of preterm brain injuries remains a significant challenge. Here, we identified subventricular zone echogenicity (SVE) on cranial ultrasound in preterm infants following intestinal perforations. The development of SVE was significantly associated with motor impairment at 2 years. SVE was replicated in a neonatal mouse model of intestinal perforation. Examination of the murine echogenic subventricular zone (SVZ) revealed NLRP3-inflammasome assembly in multiciliated FoxJ1 + ependymal cells and a loss of the ependymal border in this postnatal stem cell niche. These data suggest a mechanism of preterm brain injury localized to the SVZ that has not been adequately considered. Ultrasound detection of SVE may serve as an early biomarker for neurodevelopmental impairment after inflammatory disease in preterm infants., Competing Interests: Declaration of interests E.J.B. and S.G.G. are scientific cofounders at Tellus Therapeutics—a startup company developing therapies for neonatal brain injury. There is no intellectual property associated with this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Isolation of adult Neural Stem/Progenitor Cells (NSPCs) from their neurogenic niches, is a prerequisite for studies involving culturing of NSPCs as neurospheres or attached monolayers in vitro. The currently available protocols involve the use of multiple animals and expensive reagents to establish the NSPCs culture., New Method: This unit describes a method to isolate and culture NSPCs from the two neurogenic niches in the mouse brain, the Subventricular Zone (SVZ) and Dentate gyrus (DG)/subgranular zone (SGZ), in an easy and cost-effective manner., Results: NSPCs from SVZ and DG regions of adult mouse brains were isolated and cultured up to passage 15 without losing their stem/progenitor characteristics. These NSPCs could be differentiated into neurons, astrocytes, and oligodendrocytes, revealing its trilineage potential., Comparison With Existing Methods: This protocol eliminates the need for multiple animals as well as the use of many expensive reagents mentioned in previous protocols, adding to the cost-effectiveness of experiments. In addition, we have effectively reduced the number of steps involved in isolation and propagation, thereby minimizing the chances of contamination., Conclusion: Our simplified protocol for the isolation and culturing of adult NSPCs from the SVZ and DG demonstrates a cost-effective and efficient alternative to existing methods, reducing the need for sacrificing many animals and the usage of expensive reagents. This method permits the long-term maintenance of NSPCs' stem/progenitor characteristics and their effective differentiation into the major types of cells in the brain, making it a valuable resource for researchers in the field., Basic Protocol: Isolation and Culturing of Neural Stem/Progenitor cells from the Sub ventricular Zone and the Dentate Gyrus of the adult mouse brain. SUPPORT PROTOCOL 1: Cryopreservation, and revival of frozen NSPCs. SUPPORT PROTOCOL 2: Preparation of adherent monolayer cultures of neural stem/progenitor cells for the differentiation into multiple lineages SUPPORT PROTOCOL 3: Differentiation of NSPCs to neuronal and glial lineages SUPPORT PROTOCOL 4: Characterization of differentiated cells by immunocytochemistry., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Baby Chakrapani PS reports financial support was provided by Kerala State Council for Science Technology and Environment., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods . Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for International Journal of Clinical and Health Psychology and was not involved in the editorial review or the decision to publish this article., (© 2024 The Author(s).)

Purpose: To assess the performance of the inferior lateral ventricle (ILV) to hippocampal (Hip) volume ratio on brain MRI, for Alzheimer's disease (AD) diagnostics, comparing it to individual automated ILV and hippocampal volumes, and visual medial temporal lobe atrophy (MTA) consensus ratings., Methods: One-hundred-twelve subjects (mean age ± SD, 66.85 ± 13.64 years) with varying degrees of cognitive decline underwent MRI using a Philips Ingenia 3T. The MTA scale by Scheltens, rated on coronal 3D T1-weighted images, was determined by three experienced radiologists, blinded to diagnosis and sex. Automated volumetry was computed by icobrain dm (v. 5.10) for total, left, right hippocampal, and ILV volumes. The ILV/Hip ratio, defined as the percentage ratio between ILV and hippocampal volumes, was calculated and compared against a normative reference population (n = 1903). Inter-rater agreement, association, classification accuracy, and clinical interpretability on patient level were reported., Results: Visual MTA scores showed excellent inter-rater agreement. Ordinal logistic regression and correlation analyses demonstrated robust associations between automated brain segmentations and visual MTA ratings, with the ILV/Hip ratio consistently outperforming individual hippocampal and ILV volumes. Pairwise classification accuracy showed good performance without statistically significant differences between the ILV/Hip ratio and visual MTA across disease stages, indicating potential interchangeability. Comparison to the normative population and clinical interpretability assessments showed commensurability in classifying MTA "severity" between visual MTA and ILV/Hip ratio measurements., Conclusion: The ILV/Hip ratio shows the highest correlation to visual MTA, in comparison to automated individual ILV and hippocampal volumes, offering standardized measures for diagnostic support in different stages of cognitive decline., (© 2024. The Author(s).)

Background: Biallelic pathogenic variants in PIP5K1C (MIM #606,102) lead to lethal congenital contractural syndrome 3 (LCCS3, MIM #611,369), a rare autosomal recessive genetic disorder characterized by small gestational age, severe multiple joint contractures and muscle atrophy, early death due to respiratory failure. Currently, 5 individuals with LCCS3 were reported and 5 pathogenic variants in PIP5K1C were identified. Here, we reported the two fetuses in a Chinese pedigree who displayed multiple joint contractures and other congenital anomalies., Methods: Trio-based whole-exome sequencing (WES) was performed for the parents and the recent fetus to detect the genetic cause for fetus phenotype., Results: A novel variant, NM_012398.3: c.949_952dup, p.S318Ifs*28 and a previously reported variant, c.688_689del, p.G230Qfs*114 (ClinVar database) in PIP5K1C, were detected in the individuals, and these variants were inherited from the mother and father, respectively. We described the features of multiple joint contractures in our fetuses, including bilateral talipes equinovarus, stiffness in the limbs, extended knees, persistently closed hands and overlapping fingers, which have not been delineated detailedly in previously reported LCCS3 individuals. Furthermore, novel phenotype, bilateral dilated lateral ventricles, was revealed in one fetus., Conclusions: These findings expanded the genetic variant spectrum of PIP5K1C and enriched the clinical features of LCCS3, which will help with the prenatal diagnosis and genetic counseling for this family., (© 2024. The Author(s).)

The expression of growth/differentiation factor (GDF) 15 increases in the ganglionic eminence (GE) late in neural development, especially in neural stem cells (NSCs). However, GDF15 function in this region remains unknown. We report that GDF15 receptor is expressed apically in the GE and that GDF15 ablation promotes proliferation and cell division in the embryonic GE and in the adult ventricular-subventricular zone (V-SVZ). This causes a transient generation of additional neuronal progenitors, compensated by cell death, and a lasting increase in the number of ependymal cells and apical NSCs. Finally, both GDF15 receptor and the epidermal growth factor receptor (EGFR) were expressed in progenitors and mutation of GDF15 affected EGFR signaling. However, only exposure to exogenous GDF15, but not to EGF, normalized proliferation and the number of apical progenitors. Thus, GDF15 regulates proliferation of apical progenitors in the GE, thereby affecting the number of ependymal cells and NSCs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Germinal activity persists throughout life within the ventricular-subventricular zone (V-SVZ) of the postnatal forebrain due to the presence of neural stem cells (NSCs). Accumulating evidence points to a recruitment for these cells following early brain injuries and suggests their amenability to manipulations. We used chronic hypoxia as a rodent model of early brain injury to investigate the reactivation of cortical progenitors at postnatal times. Our results reveal an increased proliferation and production of glutamatergic progenitors within the dorsal V-SVZ. Fate mapping of V-SVZ NSCs demonstrates their contribution to de novo cortical neurogenesis. Transcriptional analysis of glutamatergic progenitors shows parallel changes in methyltransferase 14 (Mettl14) and Wnt/β-catenin signaling. In agreement, manipulations through genetic and pharmacological activation of Mettl14 and the Wnt/β-catenin pathway, respectively, induce neurogenesis and promote newly-formed cell maturation. Finally, labeling of young adult NSCs demonstrates that pharmacological NSC activation has no adverse effects on the reservoir of V-SVZ NSCs and on their germinal activity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

The volume of the lateral ventricles is a reliable and sensitive indicator of brain atrophy and disease progression in behavioural variant frontotemporal dementia. In this study, we validate our previously developed automated tool using ventricular features (known as VentRa) for the classification of behavioural variant frontotemporal dementia versus a mixed cohort of neurodegenerative, vascular and psychiatric disorders from a clinically representative independent dataset. Lateral ventricles were segmented for 1110 subjects-14 behavioural variant frontotemporal dementia, 30 other frontotemporal dementia, 70 Lewy body disease, 898 Alzheimer's disease, 62 vascular brain injury and 36 primary psychiatric disorder from the publicly accessible National Alzheimer's Coordinating Center dataset to assess the performance of VentRa. Using ventricular features to discriminate behavioural variant frontotemporal dementia subjects from primary psychiatric disorders, VentRa achieved an accuracy rate of 84%, a sensitivity rate of 71% and a specificity rate of 89%. VentRa was able to identify behavioural variant frontotemporal dementia from a mixed age-matched cohort (i.e. other frontotemporal dementia, Lewy body disease, Alzheimer's disease, vascular brain injury and primary psychiatric disorders) and to correctly classify other disorders as 'not compatible with behavioral variant frontotemporal dementia' with a specificity rate of 83%. The specificity rates against each of the other individual cohorts were 80% for other frontotemporal dementia, 83% for Lewy body disease, 83% for Alzheimer's disease, 84% for vascular brain injury and 89% for primary psychiatric disorders. VentRa is a robust and generalizable tool with potential usefulness for improving the diagnostic certainty of behavioural variant frontotemporal dementia, particularly for the differential diagnosis with primary psychiatric disorders., Competing Interests: D.L.C. is the co-founder of True Positive Medical Devices. S.D. is the co-founder of AFX Medical Inc. The other authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

In the adult mammalian brain, neurons are produced from neural stem cells (NSCs) residing in two niches-the subventricular zone (SVZ), which forms the lining of the lateral ventricles, and the subgranular zone in the hippocampus. Epigenetic mechanisms contribute to maintaining distinct cell fates by suppressing gene expression that is required for deciding alternate cell fates. Several histone deacetylase (HDAC) inhibitors can affect adult neurogenesis in vivo. However, data regarding the role of specific HDACs in cell fate decisions remain limited. Herein, we demonstrate that HDAC8 participates in the regulation of the proliferation and differentiation of NSCs/neural progenitor cells (NPCs) in the adult mouse SVZ. Specific knockout of Hdac8 in NSCs/NPCs inhibited proliferation and neural differentiation. Treatment with the selective HDAC8 inhibitor PCI-34051 reduced the neurosphere size in cultures from the SVZ of adult mice. Further transcriptional datasets revealed that HDAC8 inhibition in adult SVZ cells disturbs biological processes, transcription factor networks, and key regulatory pathways. HDAC8 inhibition in adult SVZ neurospheres upregulated the cytokine-mediated signaling and downregulated the cell cycle pathway. In conclusion, HDAC8 participates in the regulation of in vivo proliferation and differentiation of NSCs/NPCs in the adult SVZ, which provides insights into the underlying molecular mechanisms.

Background: Neuroprotection combined with neuroregeneration may be critical for optimizing functional recovery in neonatal encephalopathy. To investigate the neurogenic response to hypoxia-ischemia (HI) followed by normothermia (38.5 °C) or three different hypothermic temperatures (35, 33.5, or 30 °C) in the subventricular zone (SVZ) of the neonatal piglet., Methods: Following transient cerebral HI and resuscitation, 28 newborn piglets were randomized to: normothermia or whole-body cooling to 35 °C, 33.5 °C, or 30 °C during 2-26 h (all n = 7). At 48 h, piglets were euthanized and SVZ obtained to evaluate its cellularity, pattern of cell death, radial glia length, doublecortin (DCX, neuroblasts) expression, and Ki67 (cell proliferation) and Ki67/Sox2 (neural stem/progenitor dividing) cell counts., Results: Normothermic piglets showed lower total (Ki67+) and neural stem/progenitor dividing (Ki67+Sox2+) cell counts when compared to hypothermic groups. Cooling to 33.5 °C obtained the highest values of SVZ cellularity, radial glia length processes, neuroblast chains area and DCX immunohistochemistry. Cooling to 30 °C, however, revealed decreased cellularity in the lateral SVZ and shorter radial glia processes when compared with 33.5 °C., Conclusions: In a neonatal piglet model, hypothermia to 33.5 °C modulates the neurogenic response of the SVZ after HI, highlighting the potential beneficial effect of hypothermia to 33.5 °C on endogenous neurogenesis and the detrimental effect of overcooling beyond this threshold., Impact: Neuroprotection combined with neuroregeneration may be critical for optimizing functional recovery in neonatal encephalopathy. Hypothermia may modulate neurogenesis in the subventricular zone (SVZ) of the neonatal hypoxic-ischemic piglet. Cooling to 33.5 °C obtained the highest values of SVZ cellularity, radial glia length processes, neuroblast chains area and doublecortin immunohistochemistry; cooling to 30 °C, however, revealed decreased cellularity and shorter radial glia processes. In a neonatal piglet model, therapeutic hypothermia (33.5 °C) modulates the neurogenic response of the SVZ after hypoxia-ischemia, highlighting also the detrimental effect of overcooling beyond this threshold., (© 2023. The Author(s).)

Stereology is a discipline that allows us to obtain quantitative information about the geometric structure of three-dimensional objects. In this study, the volume of grey matter (GM), white matter (WM), and lateral ventricle (LV) of the cerebral hemispheres (CH) in sheep and goats were calculated. For this purpose, six healthy male sheep and goat brains (1-2 years old) without any anomaly were used. Brains were fixed with 10% formaldehyde in the skull. The skull was opened using standard anatomical dissection methods, and the brains were carefully removed. Brain weight and volume were measured (using Archimedes' principle) after the meninges were removed. The cerebral hemispheres were separated from the other parts of the brain by a section made in front of the rostral colliculus. In the same way, the weight and volume of the cerebral hemispheres were measured. Afterward, the cerebral hemispheres were blocked with agar, and transversal cross sections (from rostral to caudal) with an average thickness of 3.42 mm were taken from the cerebral hemispheres. Grey matter was stained with Berlin blue macroscopic staining method. The stained cross sections were scanned at 600 dpi resolution, and a point counting grid was placed on the images with the ImageJ software. Cavalieri's principle calculated the surface area and volume measurements of the grey matter, white matter, and lateral ventricle. GM, WM, and LV volumes in sheep and goat cerebral hemispheres were calculated as 54.94, 21.48 and 3.06 mL in sheep, 57.46, 24.13 and 3.12 mL in goats, respectively. The percentages of these structures in the total hemisphere volume were 71.83%, 28.17% and 4.00% in sheep, 70.42%, 29.58% and 3.82% in goats, respectively. Asymmetry was not observed in cerebral hemispheres in both species. A difference was found in the WM, LV and LV: CH ratios in the right/left comparison of the goat (p < 0.05). In comparing sheep and goats, a significant difference was observed in WM right, WM left, WM total, CH left and CH total (p < 0.05). In conclusion, the cerebral hemispheres' grey matter and white matter ratio are frequently used to diagnose neurodegenerative diseases. In recent years, the increase in neurodegenerative disease models in farm animals has been enormous. It is thought that these values obtained from healthy animals in the current study will be important for such experimental studies in the future., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

This research aims to diagnose schizophrenia with machine learning-based algorithms. Bayesian neural network, logistic regression, decision tree, k-nearest neighbor, and gaussian kernel classification techniques are investigated to diagnose schizophrenia with data from 125 persons. This study showed that left lateral ventricles and left globus pallidus volumes and their percentages in the brain were significantly lower than HCs in FEP patients. Using brain volumes, we were able to diagnose FEP with an accuracy of 73.6 % via logistic regression and with an accuracy of 86.4 % using the SVM kernel classifier method. Therefore, brain volumes can be used to diagnose FEP with the SVM kernel classifier method., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Hypoxic-ischemic brain damage (HIBD) is among the leading causes of neonatal death worldwide. miR-124-3p can be utilized as a potential diagnostic and prognostic biomarker for perinatal asphyxia and HI encephalopathy in newborns. This study investigated the protective effect and mechanism of miR-124-3p in astrocyte-derived extracellular vesicles (ADEVs) in HIBD., Methods:     The neonatal mouse model of HIBD was established. Astrocytes were transfected with the miR-124-3p inhibitor, followed by isolation and identification of ADEVs (ADEVs + inhi miR). HIBD mice were injected with ADEVs or ADEVs + inhi miR through the lateral ventricle, and neurological function was evaluated based on the modified neurological severity score (mNSS). The infarct volume of mice and the morphological modifications of neurons were observed by TTC staining and hematoxylin-eosin staining. The contents of SOD, GSH-Px, CAT, and MDA in the hippocampus were measured. The neuronal apoptosis, the activation of MPO+ neutrophils, NK cells, and CD3+ cells in CA1 region of the hippocampus was determined by means of TUNEL staining and immunofluorescence., Results: ADEVs alleviated HIBD in neonatal mice. ADEVs could intrinsically protect mice from HIBD by reducing oxidative stress and apoptosis in hippocampal tissue. ADEVs inhibited the positive expression of MPO+ neutrophils, NK cells, and CD3+ cells in HIBD neonatal mice. ADEVs inhibited the hippocampal immune cells by delivering miR-124-3p in neonatal HIBD mice., Conclusion: ADEVs can inhibit the abnormal activation of immune function in HIBD by delivering miR-124-3p, thereby eliciting a protective effect on brain damage in neonatal mice.

Microglia are the primary phagocytes in the central nervous system and clear dead cells generated during development or disease. The phagocytic process shapes the microglia phenotype, which affects the local environment. A unique population of microglia resides in the ventricular-subventricular zone (V-SVZ) of neonatal mice, but how they influence the neurogenic niche is not well understood. Here, we demonstrate that phagocytosis contributes to a pro-neurogenic microglial phenotype in the V-SVZ and that these microglia phagocytose apoptotic cells via the engulfment receptor Jedi-1. Deletion of Jedi-1 decreases apoptotic cell clearance, triggering a neuroinflammatory microglia phenotype that resembles dysfunctional microglia in neurodegeneration and aging and that reduces neural precursor proliferation via elevated interleukin-1β signaling; interleukin-1 receptor inhibition rescues precursor proliferation in vivo. Together, these results reveal a critical role for Jedi-1 in connecting microglial phagocytic activity to the maintenance of a pro-neurogenic phenotype in the developing V-SVZ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Postnatal neurogenesis has been shown to rely on the endocannabinoid system. Here we aimed at unravelling the role of Cannabidivarin (CBDV), a non-psychoactive cannabinoid, with high affinity for the non-classical cannabinoid receptor TRPV1, on subventricular zone (SVZ) postnatal neurogenesis. Using the neurosphere assay, SVZ-derived neural stem/progenitor cells (NSPCs) were incubated with CBDV and/or 5'-Iodoresinferotoxin (TRPV1 antagonist), and their role on cell viability, proliferation, and differentiation were dissected. CBDV was able to promote, through a TRPV1-dependent mechanism, cell survival, cell proliferation and neuronal differentiation. Furthermore, pulse-chase experiments revealed that CBDV-induced neuronal differentiation was a result of cell cycle exit of NSPCs. Regarding oligodendrocyte differentiation, CBDV inhibited oligodendrocyte differentiation and maturation. Since our data suggested that the CBDV-induced modulation of NSPCs acted via TRPV1, a sodium-calcium channel, and that intracellular calcium levels are known regulators of NSPCs fate and neuronal maturation, single cell calcium imaging was performed to evaluate the functional response of SVZ-derived cells. We observed that CBDV-responsive cells displayed a two-phase calcium influx profile, being the initial phase dependent on TRPV1 activation. Taken together, this work unveiled a novel and untapped neurogenic potential of CBDV via TRPV1 modulation. These findings pave the way to future neural stem cell biological studies and repair strategies by repurposing this non-psychoactive cannabinoid as a valuable therapeutic target., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier B.V.)

Olfaction is a crucial sense that is essential for the well-being and survival of individuals. Olfactory bulb (OB) is the first olfactory relay station, and its function depends on newly generated neurons from the subventricular zone (SVZ). These newly born neurons constantly migrate through the rostral migratory stream to integrate into existing neural networks within the OB, thereby contributing to olfactory information processing. However, the mechanisms underlying the contribution of SVZ adult neurogenesis to OB neurogenesis remain largely elusive. Adult neurogenesis is a finely regulated multistep process involving the proliferation of adult neural stem cells (aNSCs) and neural precursor cells, as well as the migration and differentiation of neuroblasts, and integration of newly generated neurons into preexisting neuronal circuitries. Recently, extensive studies have explored the mechanism of SVZ and OB neurogenesis. This review focused on elucidating various molecules and signaling pathways associated with OB neurogenesis dependent on the SVZ function. A better understanding of the mechanisms underlying the OB neurogenesis on the adult brain is an attractive prospect to induce aNSCs in SVZ to generate new neurons to ameliorate olfactory dysfunction that is involved in various diseases. It will also contribute to developing new strategies for the human aNSCs-based therapies., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Stroke enhances proliferation of neural precursor cells within the subventricular zone (SVZ) and induces ectopic migration of newborn cells towards the site of injury. Here, we characterize the identity of cells arising from the SVZ after stroke and uncover a mechanism through which they facilitate neural repair and functional recovery. With genetic lineage tracing, we show that SVZ-derived cells that migrate towards cortical photothrombotic stroke in mice are predominantly undifferentiated precursors. We find that ablation of neural precursor cells or conditional knockout of VEGF impairs neuronal and vascular reparative responses and worsens recovery. Replacement of VEGF is sufficient to induce neural repair and recovery. We also provide evidence that CXCL12 from peri-infarct vasculature signals to CXCR4-expressing cells arising from the SVZ to direct their ectopic migration. These results support a model in which vasculature surrounding the site of injury attracts cells from the SVZ, and these cells subsequently provide trophic support that drives neural repair and recovery., (© 2023. Springer Nature Limited.)

Lipopolysaccharide (LPS) is a natural agonist of toll-like receptor 4 that serves a role in innate immunity. The current study evaluated the LPS-mediated regulation of neurogenesis in the subventricular zone (SVZ) progenitors, that is, the basal radial glia and intermediate progenitors (IPs), in ferrets. Ferret pups were subcutaneously injected with LPS (500 μg/g of body weight) on postnatal days (PDs) 6 and 7. Furthermore, 5-ethynyl-2'-deoxyuridine (EdU) and 5-bromo-2'-deoxyuridine (BrdU) were administered on PDs 5 and 7, respectively, to label the post-proliferative and proliferating cells in the inner SVZ (iSVZ) and outer SVZ (oSVZ). A significantly higher density of BrdU single-labeled proliferating cells was observed in the iSVZ of LPS-exposed ferrets than in controls but not in post-proliferative EdU single-labeled and EdU/BrdU double-labeled self-renewing cells. BrdU single-labeled cells exhibited a lower proportion of Tbr2 immunostaining in LPS-exposed ferrets (22.2%) than in controls (42.6%) and a higher proportion of Ctip2 immunostaining in LPS-exposed ferrets (22.2%) than in controls (8.6%). The present findings revealed that LPS modified the neurogenesis of SVZ progenitors. Neonatal LPS exposure facilitates the proliferation of SVZ progenitors, followed by the differentiation of Tbr2-expressing IPs into Ctip2-expressing immature neurons.

The precise timing of neural progenitor development and the correct balance between proliferation and differentiation are crucial to generating a functional brain. The number, survival, and differentiation of neural progenitors during postnatal neurogenesis and gliogenesis is a highly regulated process. Postnatally, the majority of brain oligodendrocytes are generated from progenitors residing in the subventricular zone (SVZ), the germinal niche surrounding the lateral ventricles. In this study, we demonstrate that the p75 neurotrophin receptor (p75NTR) is highly expressed by OPCs in the postnatal male and female rat SVZ. Whereas the p75NTR is known to initiate apoptotic signaling after brain injury, it is highly expressed by proliferating progenitors in the SVZ, suggesting that it may have a different function during development. Lack of p75NTR reduced progenitor proliferation and caused premature oligodendrocyte differentiation and maturation both in vitro and in vivo, leading to aberrant early myelin formation. Our data reveal a novel role for p75NTR as a rheostat for oligodendrocyte production and maturation during myelin formation in the postnatal rat brain., (© 2023 The Authors. GLIA published by Wiley Periodicals LLC.)

Background: Hydrocephalus caused by spontaneous intracerebral hemorrhage (ICH) is an independent risk factor with adverse effects on the progression of the disease. Until now, the choice of intraventricular catheter placement and intraventricular fibrinolysis (IVF) has been mainly based on the personal experience of the neurosurgeon., Objective: We will introduce the clinical effect of the new external ventricular drainage (EVD), an independent innovation of our medical center, on ICH patients, hoping to inspire more neurosurgeons to apply our method., Methods: In this open retrospective study, We analyzed the clinical data, radiological manifestations, and prognostic scores of 10 patients with the spontaneous intracerebral hemorrhage who received transfrontal lateral ventricle puncture and drainage under laser navigation in our hospital., Results: A total of 10 patients with an average age of 58.10±9.97 years were enrolled for emergency surgery. All operations were completed according to the consensus specifications. It took 11.25±3.81 days for the intracranial pressure to return to normal. On admission, patients had a median GCS of 10. The median preoperative GCS was 8. The median GCS at discharge score was 15. At discharge, the median NIHSS score was 4. After 6 months of follow-up, patients had a median NIHSS score of 4. At discharge, the median ADL score of patients was 85. After 6 months of follow-up, the median ADL score of the patients was 95., Conclusion: In treating patients with ICH, the emergency treatment of transfrontal external ventricular drainage combined with OMMAYA sac implantation under laser navigation is a surgical method worthy of further study., Competing Interests: The author declares no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Mutaz B. Habal, MD.)

The evaluation of the different parameters of the brain ventricles is used in the diagnostics of age-related degenerative diseases of the central nervous system, as well as psychiatric disorders. The purpose of this study was to obtain data about the normal morphologic parameters of the lateral ventricles of the human brain and their relations with age and sex to establish a solid background for the diagnostics of any pathologic changes. Computed tomography (CT) studies of 108 healthy individuals aged from 17 to 86 (mean age: 46.87 ± 17.31) were selected for the study. The width of the different portions of the lateral ventricles was measured, and its relations with age and gender were assessed. The study has demonstrated a statistically significant dependence of the width of the different portions of the lateral ventricles on age. There was no statistically significant difference in this parameter identified between male and female groups. The width of the different portions of the lateral ventricles of the brain increases with age. Parameters are similar in males and females., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Zhuravlova et al.)

The transorbital approach (TOA) can provide immediate access to the lateral ventricles by piercing the roof of the orbit (ROO) with a spinal needle and without the need of a drill. Reliable external landmarks for the TOA ventriculostomy have been described, however, the necessary spinal needle gauge and other relevant parameters such as the thickness of the ROO have not been evaluated. Nineteen formalin-fixed adult cadaveric heads underwent the TOA. Spinal needles of different gauges were consecutively used in each specimen beginning with the smallest gauge until the ROO was successfully pierced. The thickness of the ROO at the puncture site and around its margins was measured. Other parameters were also measured. The TOA was successfully performed in 14 cases (73.68%), where the most suitable needle gauge was 13 (47.37%), followed by a 10-gauge needle (36.84%). The mean thickness of the ROO at the puncture site, and the mean length of the needle to the puncture site were 1.7 mm (range 0.2-3.4 mm) and 15.5 mm (range 9.2-23.4 mm), respectively. A ROO thickness of greater than 2.0 mm required a 10-gauge needle in seven cases, and in five cases, a 10-gauge needle was not sufficient for piercing the ROO. The presence of hyperostosis frontalis interna (HFI) (21.05%) was related to the failure of this procedure (80%; p < 0.00). Using a 13/10-gauge spinal needle at Tubbs' point for TOA ventriculostomy allowed for external ventricular access in most adult specimens. The presence of HFI can hinder this procedure. These findings are important when TOA ventriculostomy is considered., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: A minimally invasive option of colloid cyst surgical treatment is endoscopic resection, well validated in various reports and clinical practice. A rare complication of the surgical treatment, previously reported only once in literature, is the entrapment of the lateral ventricle. In this study we aim to outline our experience in the management of this occurrence, hypothesizing possible etiopathogenetic causes., Methods: Among patients who underwent neuroendoscopic resection for a colloid cysts at our Institution between 2013 and 2022, cases who developed a postoperative lateral ventricle entrapment were retrospectively reviewed and included. Clinical history, imaging and treatment were reported., Results: Among 34 patients treated for a colloid cysts, two (5.9 %) patients developed an ipsilateral ventricular entrapment with dilation from two to five months after the resection. Both patients were substantially asymptomatic and neurologically intact, and therefore treated conservatively. One case underwent complete spontaneous radiological resolution one month later, and the other one has remained neurological asymptomatic at follow-up., Conclusions: Isolated asymptomatic ventricular entrapment with significant dilation after endoscopic colloid cyst resection is a rare occurrence which can be plausibly caused by scar tissue at the level of the foramen of Monro. Because they can have an indolent course with spontaneous resolution, conservative treatment is a viable option, with strict radiological and clinical follow - up. Given the rarity of the occurrence, further studies with larger cohorts are warranted to confirm the etiopathogenetic hypothesis and validate the clinical management., (Copyright © 2023 Elsevier B.V. All rights reserved.)

N-butyl cyanoacrylate (NBCA) has been used to embolise brain arteriovenous malformations (AVMs) for over 30 years. It is a mixed with lipiodol in varying proportions. We report a 22-year-old male with intraventricular hemorrhage from a ruptured intranidal AVM aneurysm in the left temporal lobe. The intranidal aneurysm and the nidus were successfully embolized using a 20% NBCA and lipiodol mixture without any complications according to computed tomography (CT) immediately after treatment. Scattered high-density spots were observed in both lateral ventricles on CT 5 days after embolization, suggesting migration of lipiodol. We speculated that the aneurysm was a pseudoaneurysm whose wall protruded into the inferior horn of the left lateral ventricle, and the lipiodol in the NBCA migrated into the ventricles after the thin part of the wall ruptured. The patient developed pyrexia due to chemical meningitis, which responded to steroid treatment for one month.

Neurogenesis and differentiation of neural stem cells (NSCs) are controlled by cell-intrinsic molecular pathways that interact with extrinsic signaling cues. In this study, we identify a circuit that regulates neurogenesis and cell proliferation in the lateral ventricle-subventricular zone (LV-SVZ). Our results demonstrate that direct glutamatergic projections from the anterior cingulate cortex (ACC), as well as inhibitory projections from calretinin + local interneurons, modulate the activity of cholinergic neurons in the subependymal zone (subep-ChAT + ). Furthermore, in vivo optogenetic stimulation and inhibition of the ACC-subep-ChAT + circuit are sufficient to control neurogenesis in the ventral SVZ. Both subep-ChAT + and local calretinin + neurons play critical roles in regulating ventral SVZ neurogenesis and LV-SVZ cell proliferation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Subependymomas are World Health Organization grade I tumors, and 30% occur in the lateral ventricles. Surgery is the mainstay of treatment, and the transcallosal or transcortical/transsulcal approaches are preferred for those tumors occurring near the foramen of Monro or atrium. Visualization, proximity to the fornix and basal ganglia, hydrocephalus, and brain retraction during surgery make these operations challenging. The authors present the case of a 65-year-old male with a subependymoma located in the left lateral ventricle. The tumor was completely resected using an interhemispheric/transcallosal approach., Observations: The authors analyze the anatomopathological features of subependymoma, along with the clinical behavior and therapeutic options. The authors discuss in detail the advantages and disadvantages of the interhemispheric/transcallosal approach for resection of these tumors., Lessons: Subependymomas are slow-growing lesions with an indolent yet complicated course making surgical removal challenging yet feasible using the correct techniques. The interhemispheric transcallosal approach offers an excellent route for the resection of large subependymomas, but there is still a significant risk for postoperative complications.

Objective: To investigate the value of histogram parameters in quantifying brain development trajectory at slice of anterior and posterior horns of lateral ventricles on conventional brain MRI in normal children aged 0-5 years. Methods: Routine brain MRI data [apparent diffusion coefficient (ADC) map, T 1 -weighted imaging (T 1 WI), and T 2 -weighted imaging (T 2 WI)] were retrospectively collected from 300 children aged 0-5 years who underwent MRI at Children 's Hospital of Nanjing Medical University from April 2014 to November 2021, 154 males and 146 females, aged [ M ( Q 1 , Q 3 =60) in a ratio of 8∶2. The training set was divided into 6 groups according to age:≤0.5 years, 24 persons; >0.5-≤1 years,21 persons; >1-≤2 years,31 persons; >2-≤3 years,44 persons; >3-≤4 years,42 persons; >4-≤5 years,78 persons. MRIcron software was used to delineate the whole brain at the level of the anterior and posterior horns of the lateral ventricles of the three MRI data as the region of interest. Then gray histograms and their parameters [including mean, maximum, minimum, skewness, kurtosis, mode, variance, and percentiles at 5% intervals from 10% to 95%(10th-95th) ]were obtained. Intra-class correlation coefficients (ICC) were used to assess consistency of intra-observer and inter-observer measurement. Representative parameters were selected by Spearman correlation analysis and curve fitting. The linear regression coefficient β represented development rates at different ages. The selected curve regression models were applied to the validation set, and the reliability of the model was evaluated with accuracy. n =240) and validation set ( n =60) in a ratio of 8∶2. The training set was divided into 6 groups according to age:≤0.5 years, 24 persons; >0.5-≤1 years,21 persons; >1-≤2 years,31 persons; >2-≤3 years,44 persons; >3-≤4 years,42 persons; >4-≤5 years,78 persons. MRIcron software was used to delineate the whole brain at the level of the anterior and posterior horns of the lateral ventricles of the three MRI data as the region of interest. Then gray histograms and their parameters [including mean, maximum, minimum, skewness, kurtosis, mode, variance, and percentiles at 5% intervals from 10% to 95%(10th-95th) ]were obtained. Intra-class correlation coefficients (ICC) were used to assess consistency of intra-observer and inter-observer measurement. Representative parameters were selected by Spearman correlation analysis and curve fitting. The linear regression coefficient β represented development rates at different ages. The selected curve regression models were applied to the validation set, and the reliability of the model was evaluated with accuracy. Results: Intra-observer and inter-observer histogram measurement parameters were generally in good consistency (ICC>0.800, all P <0.001). Histogram parameters ADC 10th-65th, T 1 WI 55th-80th and T 2 WI 10th-45th were highly correlated with age (∣ r ∣≥0.700, 0.600 and 0.600 respectively; all P <0.001). ADC 30th and T 2 WI 10th had the greatest goodness of fit ( R ²=0.871, 0.873; both P <0.001). Map of brain development trends showed that ADC 30th and T 2 WI 10th decreased with age. ADC 30th changed rapidly before the age of 2 years, most significantly within 6 months, and the rate of decrease slowed down after 2 years old. T 2 Histogram parameters can quantify brain developmental trajectories at slice of anterior and posterior horns of lateral ventricles on conventional MRI in normal children aged 0-5 years, and obtain the brain development curves reflecting this slice of this age group.2 WI 10th had higher accuracy in validation set [93% (56/60) and 95% (57/60), respectively]. Conclusion: Histogram parameters can quantify brain developmental trajectories at slice of anterior and posterior horns of lateral ventricles on conventional MRI in normal children aged 0-5 years, and obtain the brain development curves reflecting this slice of this age group.

Neural progenitor cells (NPCs) are multipotent neural stem cells (NSCs) capable of self-renewing and differentiating into neurons, astrocytes and oligodendrocytes. In the postnatal/adult brain, NPCs are primarily located in the subventricular zone (SVZ) of the lateral ventricles (LVs) and subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). There is evidence that NPCs are also present in the postnatal/adult hypothalamus, a highly conserved brain region involved in the regulation of core homeostatic processes, such as feeding, metabolism, reproduction, neuroendocrine integration and autonomic output. In the rodent postnatal/adult hypothalamus, NPCs mainly comprise different subtypes of tanycytes lining the wall of the 3 rd ventricle. In the postnatal/adult human hypothalamus, the neurogenic niche is constituted by tanycytes at the floor of the 3 rd ventricle, ependymal cells and ribbon cells (showing a gap-and-ribbon organization similar to that in the SVZ), as well as suprachiasmatic cells. We speculate that in the postnatal/adult human hypothalamus, neurogenesis occurs in a highly complex, exquisitely sophisticated neurogenic niche consisting of at least four subniches; this structure has a key role in the regulation of extrahypothalamic neurogenesis, and hypothalamic and extrahypothalamic neural circuits, partly through the release of neurotransmitters, neuropeptides, extracellular vesicles (EVs) and non-coding RNAs (ncRNAs).

Neurogenesis, the formation of new neurons in the brain, occurs throughout the lifespan in the subgranular zone of the dentate gyrus and subventricular zone (SVZ) lining the lateral ventricles of the mammal brain. In this process, gamma-aminobutyric acid (GABA) and its ionotropic receptor, the GABA A receptor (GABA A R), play a critical role in the proliferation, differentiation, and migration process of neural stem/progenitor cells (NPC). Taurine, a non-essential amino acid widely distributed throughout the central nervous system, increases the proliferation of SVZ progenitor cells by a mechanism that may involve GABA A R activation. Therefore, we characterized the effects of taurine on the differentiation process of NPC expressing GABA A R. Preincubation of NPC-SVZ with taurine increased microtubule-stabilizing proteins assessed with the doublecortin assay. Taurine, like GABA, stimulated a neuronal-like morphology of NPC-SVZ and increased the number and length of primary, secondary, and tertiary neurites compared with control NPC of the SVZ. Furthermore, neurite outgrowth was prevented when simultaneously incubating cells with taurine or GABA and the GABA A R blocker, picrotoxin. Patch-clamp recordings revealed a series of modifications in the NPCs' passive and active electrophysiological properties exposed to taurine, including regenerative spikes with kinetic properties similar to the action potentials of functional neurons., (© 2023. The Author(s).)

Progressive white matter degeneration in periventricular and deep white matter regions appears as white matter hyperintensities (WMH) on MRI scans. To date, periventricular WMHs are often associated with vascular dysfunction. Here, we demonstrate that ventricular inflation resulting from cerebral atrophy and hemodynamic pulsation with every heartbeat leads to a mechanical loading state of periventricular tissues that significantly affects the ventricular wall. Specifically, we present a physics-based modeling approach that provides a rationale for ependymal cell involvement in periventricular WMH formation. Building on eight previously created 2D finite element brain models, we introduce novel mechanomarkers for ependymal cell loading and geometric measures that characterize lateral ventricular shape. We show that our novel mechanomarkers, such as maximum ependymal cell deformations and maximum curvature of the ventricular wall, spatially overlap with periventricular WMH locations and are sensitive predictors for WMH formation. We also explore the role of the septum pellucidum in mitigating mechanical loading of the ventricular wall by constraining the radial expansion of the lateral ventricles during loading. Our models consistently show that ependymal cells are stretched thin only in the horns of the ventricles irrespective of ventricular shape. We therefore pose that periventricular WMH etiology is strongly linked to the deterioration of the over-stretched ventricular wall resulting in CSF leakage into periventricular white matter. Subsequent secondary damage mechanisms, including vascular degeneration, exacerbate lesion formation and lead to progressive growth into deep white matter regions., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Johannes Weickenmeier reports financial support was provided by National Institutes of Health. Henry Rusinek reports financial support was provided by National Institutes of Health., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: While CSF diversion is highly effective at treating hydrocephalus, shunting is unfortunately associated with a very high revision rate. Studies have demonstrated that proximal catheter obstruction is a major cause of failure. A novel proximal access device was developed, and pilot testing was performed in a sheep model of hydrocephalus., Methods: Hydrocephalus was induced in 8 sheep using a cisternal injection of 4 ml of 25% kaolin, and the sheep were randomized to either a standard ventricular catheter or a novel intraparenchymal stent (IPS). Both groups received identical valves and distal catheters. The novel device included a 3D-printed stainless steel port and a 6 × 40-mm covered peripheral vascular stent. Animals were euthanized for signs of hydrocephalus or at a time point of 2 months. MRI was performed to determine ventricular size. Time to failure and Evans indices were compared using the Wilcoxon rank-sum test., Results: All 4 experimental devices were placed without difficulty into the right lateral ventricle. There was a trend toward longer survival in the experimental group (40 vs 26 days, p = 0.24). Within the IPS group, 3 of the 4 sheep did not experience clinical symptoms of shunt failure and had an average of 37% decrease in Evans index. While 3 of 4 traditional proximal catheters demonstrated debris within the inlet holes, there was no obstructive material found in the IPSs., Conclusions: An IPS was successfully used to treat hydrocephalus in a sheep model. While statistical significance was not achieved, there were clear benefits to using a stent, including a decreased clog rate and the ability to perform a percutaneous revision. Further testing is needed to ensure efficacy and safety prior to human application.

In the postnatal brain, three regions show high mitotic activity. These brain areas are neurogenic niches, and each niche harbors a microenvironment favorable for the proliferation and differentiation of neural stem cells. These multipotential cells maintain the capacity to self-renew and generate intermediate precursors that will differentiate into neuronal and glial lineages (astrocytes and oligodendrocytes). The most well-studied niches are the ventricular-subventricular zone (V-SVZ) of the lateral ventricles, the subgranular zone (SGZ) of the dentate gyrus in the hippocampus, and the subcallosal zone (SCZ), located in the limit between the corpus callosum and the hippocampal formation. The discovery of these three neurogenic niches has gained much interest in the field because they may be a therapeutic alternative in neural regeneration and neurodegenerative disorders. In this review, we describe in brief all these regions and explain their potential impact on solving some neurological conditions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Breed traits seem to influence the dimensions of the cerebral ventricles in dogs. The ratios between the ventricles and the brain are crucial diagnostic criteria for suspected canine cognitive dysfunction (CCD). This study aimed to establish linear computed tomography (CT)-scan measurements of the cerebral ventricles in 55 Poodle dogs aged >7 years. To this end, cross-sectional CT images were evaluated. The measurements in the whole sample were: height of the right ventricle, 6.0 ± 1.6 mm; height of the left ventricle, 5.8 ± 1.6 mm; width of the right ventricle, 6.9 ± 1.4 mm; width of the left ventricle, 7.0 ± 1.3 mm; height of the third ventricle, 3.4 ± 0.8 mm; height of the right cerebral hemisphere, 39.5 ± 2.0 mm; and height of the left cerebral hemisphere, 40.2 ± 2.6 mm. The average ventricular measurements were higher in dogs older than 11 years (p < 0.05). However, the average ratio of the ventricle height to the height of the brain did not reveal differences between age groups, sex, or antimeres. In addition, none of the images showed fused lateral ventricles. Thus, these data can assist in interpreting ventricle size in senile Poodle dogs (aged >7 years)., Competing Interests: Conflict of interests: The authors declare that they have no conflicts of interest.

Manual segmentation, which is tedious, time-consuming, and operator-dependent, is currently used as the gold standard to validate automatic and semiautomatic methods that quantify geometries from 2D and 3D MR images. This study examines the accuracy of manual segmentation and generalizes a strategy to eliminate its use. Trained individuals manually measured MR lateral ventricles images of normal and hydrocephalus infants from 1 month to 9.5 years of age. We created 3D-printed models of the lateral ventricles from the MRI studies and accurately estimated their volume by water displacement. MRI phantoms were made from the 3D models and images obtained. Using a previously developed artificial intelligence (AI) algorithm that employs four features extracted from the images, we estimated the ventricular volume of the phantom images. The algorithm was certified when discrepancies between the volumes-gold standards-yielded by the water displacement device and those measured by the automation were smaller than 2%. Then, we compared volumes after manual segmentation with those obtained with the certified automation. As determined by manual segmentation, lateral ventricular volume yielded an inter and intra-operator variation up to 50% and 48%, respectively, while manually segmenting saggital images generated errors up to 71%. These errors were determined by direct comparisons with the volumes yielded by the certified automation. The errors induced by manual segmentation are large enough to adversely affect decisions that may lead to less-than-optimal treatment; therefore, we suggest avoiding manual segmentation whenever possible., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yepes-Calderon, McComb. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The mammalian adult brain contains two neural stem and precursor (NPC) niches: the subventricular zone [SVZ] lining the lateral ventricles and the subgranular zone [SGZ] in the hippocampus. From these, SVZ NPCs represent the largest NPC pool. While SGZ NPCs typically only produce neurons and astrocytes, SVZ NPCs produce neurons, astrocytes and oligodendrocytes throughout life. Of particular importance is the generation and replacement of oligodendrocytes, the only myelinating cells of the central nervous system (CNS). SVZ NPCs contribute to myelination by regenerating the parenchymal oligodendrocyte precursor cell (OPC) pool and by differentiating into oligodendrocytes in the developing and demyelinated brain. The neurosphere assay has been widely adopted by the scientific community to facilitate the study of NPCs in vitro. Here, we present a streamlined protocol for culturing postnatal and adult SVZ NPCs and OPCs from primary neurosphere cells. We characterize the purity and differentiation potential as well as provide RNA-sequencing profiles of postnatal SVZ NPCs, postnatal SVZ OPCs and adult SVZ NPCs. We show that primary neurospheres cells generated from postnatal and adult SVZ differentiate into neurons, astrocytes and oligodendrocytes concurrently and at comparable levels. SVZ OPCs are generated by subjecting primary neurosphere cells to OPC growth factors fibroblast growth factor (FGF) and platelet-derived growth factor-AA (PDGF-AA). We further show SVZ OPCs can differentiate into oligodendrocytes in the absence and presence of thyroid hormone T3. Transcriptomic analysis confirmed the identities of each cell population and revealed novel immune and signalling pathways expressed in an age and cell type specific manner., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The survival of preterm infants has improved over the last decade, but impaired brain development leading to poor neurological outcomes is still a major comorbidity associated with prematurity. The aim of this study was to evaluate the effect of nutrition on neurodevelopment in preterm infants and identify markers for improved outcomes., Methods: Totally 67 premature infants with a gestational age of 24-34 weeks and a birth weight of 450-2085 g were included. Clinical parameters and documented diet were collected from medical records. The nutritional analysis comprised the protein, fat, carbohydrate, and energy intake during different time spans. Brain development was assessed by determining deep gray matter (DGM; basal ganglia and thalamus) and lateral ventricular (LV) volumes as measured on cerebral magnetic resonance imaging scans obtained at term-equivalent age (TEA), and potential associations between nutrition and brain volumetrics were detected by regression analysis., Results: We observed a negative correlation between mean daily protein intake in the third postnatal week and MRI-measured DGM volume at TEA (P = 0.007). In contrast, head circumference at a corrected age of 35 weeks gestation (P < 0.001) and mean daily fat intake in the fourth postnatal week (P = 0.004) were positively correlated with DGM volume. Moreover, mean daily carbohydrate intake in the first postnatal week (P = 0.010) and intraventricular hemorrhage (P = 0.003) were revealed as independent predictors of LV volume., Conclusion: The study emphasizes the importance of nutrition for brain development following preterm birth., (© 2023. The Author(s).)

The subventricular zone (SVZ) is the largest neural stem cell (NSC) niche in the adult brain; herein, the blood-brain barrier is leaky, allowing direct interactions between NSCs and endothelial cells (ECs). Mechanisms by which direct NSC-EC interactions in the adult SVZ control NSC behavior are unclear. We found that Cx43 is highly expressed by SVZ NSCs and ECs, and its deletion in either leads to increased NSC proliferation and neuroblast generation, suggesting that Cx43-mediated NSC-EC interactions maintain NSC quiescence. This is further supported by single-cell RNA sequencing and in vitro studies showing that ECs control NSC proliferation by regulating expression of genes associated with NSC quiescence and/or activation in a Cx43-dependent manner. Cx43 mediates these effects in a channel-independent manner involving its cytoplasmic tail and ERK activation. Such insights inform adult NSC regulation and maintenance aimed at stem cell therapies for neurodegenerative disorders., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cerebrospinal fluid (CSF) production and absorption concept significantly changed in the early 2010s from "third circulation theory" and "classical bulk flow theory" to a whole new one as follows: First, CSF is mainly produced from interstitial fluid excreted from the brain parenchyma, and CSF produced from the choroid plexus plays an important role in maintaining brain homeostasis. Second, CSF is not absorbed in the venous sinus via the arachnoid granules, but mainly in the dural lymphatic vessels. Finally, the ventricles and subarachnoid spaces have several compensatory direct CSF pathways at the borders attached to the choroid plexus, e.g., the inferior choroidal point of the choroidal fissure, other than the foramina of Luschka and Magendie. In idiopathic normal pressure hydrocephalus (iNPH), the lateral ventricles and basal cistern are enlarged simultaneously due to the compensatory direct CSF pathways. The average total intracranial CSF volume increased from about 150 mL at 20 years to about 350 mL at 70 years due to the decrease in brain volume with aging and further increased above 400 mL in patients with iNPH. CSF movements are composed of a steady microflow produced by the rhythmic wavy movement of motile cilia on the ventricular surface and dynamic pulsatile flow produced by the brain and cerebral artery pulsation, respiration, and head movement. Pulsatile CSF movements might totally decrease with aging, but it in the ventricles might increase at the foramina of Magendie and Luschka dilation. Aging CSF dynamics are strongly associated with ventricular dilatation in iNPH.

The human brain has a highly complex structure both on the microscopic and on the macroscopic scales. Increasing evidence has suggested the role of mechanical forces for cortical folding - a classical hallmark of the human brain. However, the link between cellular processes at the microscale and mechanical forces at the macroscale remains insufficiently understood. Recent findings suggest that an additional proliferating zone, the outer subventricular zone (OSVZ), is decisive for the particular size and complexity of the human cortex. To better understand how the OSVZ affects cortical folding, we establish a multifield computational model that couples cell proliferation in different zones and migration at the cell scale with growth and cortical folding at the organ scale by combining an advection-diffusion model with the theory of finite growth. We validate our model based on data from histologically stained sections of the human fetal brain and predict 3D pattern formation. Finally, we address open questions regarding the role of the OSVZ for the formation of cortical folds. The presented framework not only improves our understanding of human brain development, but could eventually help diagnose and treat neuronal disorders arising from disruptions in cellular development and associated malformations of cortical development., Competing Interests: MZ, IB, SB No competing interests declared, (© 2023, Zarzor et al.)

Various brain regions/nuclei project axons to the subventricular zone (SVZ), a postnatal neurogenic niche. In adults, neurogenesis is controlled by neuronal activity, via neurotransmitters. Glutamate is a major excitatory neurotransmitter, and glutamate receptors are expressed in SVZ cells. Although the cerebral cortex is a major source of glutamate and the medial cortex projects axons to the medial striatum next to the SVZ, it remains unclear whether cortical neurons regulate adult neurogenesis in vivo. First, to analyze axonal projection, plasmid vector expressing DsRed was introduced to the medial cortex by in utero electroporation. At the adult stage, DsRed-labeled axons were detected in the dorsolateral, striatal, and septal areas of the SVZ, and where they were in contact with neuroblasts. Furthermore, maturation of the cortical projection and the SVZ appeared to synchronize during postnatal stages. Next, stab injuries were made in the bilateral medial cortex to interrupt cortical input to the SVZ. At 17 days post-injury, cell proliferation in the SVZ and tangential migration of neuroblasts to the olfactory bulb were not significantly affected. There were clusters of neuroblasts in the striatum close to the SVZ in all experimental groups, but the number and size of neuroblast clusters were significantly larger in the medial cortex-injured group compared with the other experimental groups. These neuroblast clusters had a morphology of tangentially migrating cells to the olfactory bulb. These results suggest that cortical input to the SVZ inhibits the radial migration of neuroblasts to converge with the migration pathway in vivo., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: In the cerebrospinal fluid (CSF) dynamics, the pulsations of cerebral arteries and brain is considered the main driving force for the reciprocating bidirectional CSF movements. However, measuring these complex CSF movements on conventional flow-related MRI methods is difficult. We tried to visualize and quantify the CSF motion by using intravoxel incoherent motion (IVIM) MRI with low multi-b diffusion-weighted imaging., Methods: Diffusion-weighted sequence with six b values (0, 50, 100, 250, 500, and 1000 s/mm 2 ) was performed on 132 healthy volunteers aged ≥ 20 years and 36 patients with idiopathic normal pressure hydrocephalus (iNPH). The healthy volunteers were divided into three age groups (< 40, 40 to < 60, and ≥ 60 years). In the IVIM analysis, the bi-exponential IVIM fitting method using the Levenberg-Marquardt algorithm was adapted. The average, maximum, and minimum values of ADC, D, D*, and fraction of incoherent perfusion (f) calculated by IVIM were quantitatively measured in 45 regions of interests in the whole ventricles and subarachnoid spaces., Results: Compared with healthy controls aged ≥ 60 years, the iNPH group had significantly lower mean f values in all the parts of the lateral and 3rd ventricles, whereas significantly higher mean f value in the bilateral foramina of Luschka. In the bilateral Sylvian fossa, which contain the middle cerebral bifurcation, the mean f values increased gradually with increasing age, whereas those were significantly lower in the iNPH group. In the 45 regions of interests, the f values in the bilateral foramina of Luschka were the most positively correlated with the ventricular size and indices specific to iNPH, whereas that in the anterior part of the 3rd ventricle was the most negatively correlated with the ventricular size and indices specific to iNPH. Other parameters of ADC, D, and D* were not significantly different between the two groups in any locations., Conclusions: The f value on IVIM MRI is useful for evaluating small pulsatile complex motion of CSF throughout the intracranial CSF spaces. Patients with iNPH had significantly lower mean f values in the whole lateral ventricles and 3rd ventricles and significantly higher mean f value in the bilateral foramina of Luschka, compared with healthy controls aged ≥ 60 years., (© 2023. The Author(s).)

Approaches to investigate adult oligodendrocyte progenitor cells (OPCs) by targeted cell ablation in the rodent CNS have limitations in the extent and duration of OPC depletion. We have developed a pharmacogenetic approach for conditional OPC ablation, eliminating >98% of OPCs throughout the brain. By combining recombinase-based transgenic and viral strategies for targeting OPCs and ventricular-subventricular zone (V-SVZ)-derived neural precursor cells (NPCs), we found that new PDGFRA-expressing cells born in the V-SVZ repopulated the OPC-deficient brain starting 12 days after OPC ablation. Our data reveal that OPC depletion induces V-SVZ-derived NPCs to generate vast numbers of PDGFRA + NG2 + cells with the capacity to proliferate and migrate extensively throughout the dorsal anterior forebrain. Further application of this approach to ablate OPCs will advance knowledge of the function of both OPCs and oligodendrogenic NPCs in health and disease., Competing Interests: The authors declare no competing interests.

The adult rodent subventricular zone (SVZ) generates neural stem cells (NSCs) throughout life that migrate to the olfactory bulbs (OBs) and differentiate into olfactory interneurons. Few SVZ NSCs generate oligodendrocyte precursor cells (OPCs). We investigated how neurogliogenesis is regulated during aging in mice and in a non-human primate (NHP) model, the gray mouse lemur. In both species, neuronal commitment decreased with age, while OPC generation and myelin content unexpectedly increased. In the OBs, more tyrosine hydroxylase interneurons in old mice, but fewer in lemurs, marked a surprising interspecies difference that could relate to our observation of a continuous ventricle in lemurs. In the corpus callosum, aging promoted maturation of OPCs into mature oligodendrocytes in mice but blocked it in lemurs. The present study highlights similarities and dissimilarities between rodents and NHPs, revealing that NHPs are a more relevant model than mice to study the evolution of biomarkers of aging., Competing Interests: Conflict of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)