Subependymal Layer Research Articles

Morphological Сharacterization of the Spinal Cord Regeneration in Adult Desert Killifish Aphaniops hormuzensis (Aphaniidae)

Morphological characterization of the lumbar spinal cord regeneration process was investigated in killifish A. hormuzensis, by using hematoxylin-eosin staining after spinal cord injury. An spinal cord injury was settled, and the injured tissue was sampled. Immediately after the spinal cord injury, the blood clot formation was detected at the injury epicenter and the ependymal layer, and at six hours post-injury (6 hpi), the inflammation and cavity formation occurred. The neural cell accumulation and beginning signs of the spinal cord regeneration were detected one-day post-injury (1 dpi) close to the ependymal layer and subependymal layer. In two 2 dpi, the tissue repair and regeneration progress were detected. The reformation of the ependymal canal happened at 3 dpi, followed by the completion of spinal cord regeneration at 5 dpi. The spinal cord regeneration potency in A. hormuzensis is relatively higher than in other traditional fish models. Studies on the regeneration of this interesting fish are new, therefore, further investigations are needed to explore additional information about various aspects of tissue regeneration. This study is important because killifishes have a short life span, show high environmental variation tolerance, and are easy to maintain and breed in laboratory conditions.

Exacerbation of chronic arachnoiditis as one of the causes of transient headache

Arachnoiditis is an organic lesion of the brain, manifested as diffuse productive inflammation in the arachnoid membrane of the brain with the formation of adhesions and cysts, involving the pia mater, ependyma and subependymal layer of the ventricles and choroid plexuses in the pathological process. The incidence of the disease is approximately 3–5 % among all organic lesions of the central nervous system. Arachnoiditis can be autoimmune in nature, the pathogenesis of which is hyperproduction of autoantibodies followed by hyperplasia of the arachnoid endothelium as a result of their effect, or manifest itself as residual manifestations after a neuroinfection or traumatic brain injury. In most cases, focal symptoms accompanying arachnoiditis are associated with irritant action and involvement of the underlying brain structures in the adhesive process. The clinical picture is a complex symptom complex, including a combination of general infectious, cerebral, focal symptoms and signs of changes in the composition of the cerebrospinal fluid. Of the cerebral symptoms, headache comes first; it occurs in 80 % of patients with a history of arachnoiditis. The greatest intensity of the headache is noted in the early morning hours; very often it is accompanied by nausea and vomiting. In the vast majority of cases, this pain is based on intracranial hypertension. In addition to headaches, non-systemic dizziness is observed, and autonomic dysfunction and increased sensory excitability are noted in those suffering from chronic arachnoiditis.

High-Fat Diet Impairs Mouse Median Eminence: A Study by Transmission and Scanning Electron Microscopy Coupled with Raman Spectroscopy.

Hypothalamic dysfunction is an initial event following diet-induced obesity, primarily involving areas regulating energy balance such as arcuate nucleus (Arc) and median eminence (ME). To gain insights into the early hypothalamic diet-induced alterations, adult CD1 mice fed a high-fat diet (HFD) for 6 weeks were studied and compared with normo-fed controls. Transmission and scanning electron microscopy and histological staining were employed for morphological studies of the ME, while Raman spectroscopy was applied for the biochemical analysis of the Arc-ME complex. In HFD mice, ME β2-tanycytes, glial cells dedicated to blood-liquor crosstalk, exhibited remarkable ultrastructural anomalies, including altered alignment, reduced junctions, degenerating organelles, and higher content of lipid droplets, lysosomes, and autophagosomes. Degenerating tanycytes also displayed an electron transparent cytoplasm filled with numerous vesicles, and they were surrounded by dilated extracellular spaces extending up to the subependymal layer. Consistently, Raman spectroscopy analysis of the Arc-ME complex revealed higher glycogen, collagen, and lipid bands in HFD mice compared with controls, and there was also a higher band corresponding to the cyanide group in the former compared to the last. Collectively, these data show that ME β2-tanycytes exhibit early structural and chemical alterations due to HFD and reveal for the first-time hypothalamic cyanide presence following high dietary lipids consumption, which is a novel aspect with potential implications in the field of obesity.

Transcriptome Response and Spatial Pattern of Gene Expression in the Primate Subventricular Zone Neurogenic Niche After Cerebral Ischemia.

The main stem cell niche for neurogenesis in the adult mammalian brain is the subventricular zone (SVZ) that extends along the cerebral lateral ventricles. We aimed at characterizing the initial molecular responses of the macaque monkey SVZ to transient, global cerebral ischemia. We microdissected tissue lining the anterior horn of the lateral ventricle (SVZa) from 7 day post-ischemic and sham-operated monkeys. Transcriptomics shows that in ischemic SVZa, 541 genes were upregulated and 488 genes were down-regulated. The transcription data encompassing the upregulated genes revealed a profile typical for quiescent stem cells and astrocytes. In the primate brain the SVZ is morphologically subdivided in distinct and separate ependymal and subependymal regions. The subependymal contains predominantly neural stem cells (NSC) and differentiated progenitors. To determine in which SVZa region ischemia had evoked transcriptional upregulation, sections through control and ischemic SVZa were analyzed by high-throughput in situ hybridization for a total of 150 upregulated genes shown in the www.monkey-niche.org image database. The majority of the differentially expressed genes mapped to the subependymal layers on the striatal or callosal aspect of the SVZa. Moreover, a substantial number of upregulated genes was expressed in the ependymal layer, implicating a contribution of the ependyma to stem cell biology. The transcriptome analysis yielded several novel gene markers for primate SVZa including the apelin receptor that is strongly expressed in the primate SVZa niche upon ischemic insult.

Subependymal hyperintense layer on CISS sequence: An MRI study.

The present study aimed to explore the subependymal layers overlying the cerebral ventricles using magnetic resonance imaging. A total of 69 outpatients underwent constructive interference in steady-state (CISS) sequence in thin-sliced, coronal, and sagittal sections. The subependymal layers were delineated as linear hyperintensities, coursing along the outer margins of the ventricular walls. On coronal images, the hyperintensities surrounding the anterior horn of the lateral ventricle were identified in 97% of patients, while those of the third ventricle were identified in 96% of patients. In the trigone and posterior horn of the lateral ventricle, the hyperintensities were delineated in all patients. On sagittal images, subependymal hyperintensities were identified in all. At the level of the anterior horn and third ventricle, the subependymal hyperintensities were found to communicate with the Virchow-Robin spaces (VRSs) in 68% and 65% of patients, respectively. At the level of the trigone and posterior horn of the lateral ventricle, the VRSs communicated with the subependymal hyperintensities in 83% of patients. Subependymal hyperintensity may represent an inflow passage of the VRSs that jointly contribute to efficient transependymal migration of the interstitial fluid into the ventricular cerebrospinal fluid.

Imaging characteristics of adult H3 K27M-mutant gliomas.

H3 K27M-mutant gliomas present heterogeneously in terms of pathology, imaging, and prognosis. This study aimed to summarize the imaging characteristics of adult H3 K27M-mutant gliomas. The authors retrospectively identified all cases of glioma diagnosed using histopathological studies (n = 3300) that tested positive for histone H3 K27M mutations (n = 75) between January 2016 and December 2018 in a single hospital. Preoperative and follow-up MR images of 66 adult patients (age ≥ 18 years) were reviewed for anatomical location, degree of contrast enhancement, enhancement patterns, hemorrhage, edema, diffusion restriction, tumor dissemination, and tumor spread. The study included 66 cases (40 in men, 26 in women) of H3 K27M-mutant glioma in adult patients. Tumors were found in the following sites: thalamus (n = 38), brainstem (n = 6), brainstem with cerebellar or thalamic involvement (n = 4), whole brain (n = 8), corpus callosum (n = 3), hypothalamus (n = 1), hemispheres (n = 2), and spinal cord (n = 4). All pure brainstem lesions were located posteriorly, and all corpus callosal lesions were in the genu. Most spinal tumors were long-segment lesions. Hemispheric lesions mimicked gliomatosis cerebri in presentation, with the addition of traditional midline structure involvement. Most tumors were solid with relatively uniform signals on plain MRI. Of the 61 cases with contrast-enhanced MR images, 36 (59%) showed partial to no enhancement, whereas 25 (41%) showed diffuse or irregular peripheral enhancement. Hemorrhage and edema were rare. Most lesions were solid and showed mild diffusion restriction on diffusion-weighted imaging. Tumor dissemination to the leptomeninges (n = 8) and subependymal layer (n = 3) was observed. The authors described the MRI features of diffuse midline glioma with H3 K27M mutation in the largest study done to date in adult patients. Tumors were found in both midline and nonmidline structures, with the thalamus being the most common site. Although adult H3 K27M-mutant gliomas demonstrated highly variable presentations in this cohort of patients, the authors were able to observe shared characteristics within each location.

Porencephaly and Periventricular Encephalitis in a 4-month-old Puppy: Detection of Canine Parvovirus Type 2 and Potential Role in Brain Lesions

A 4-month-old puppy died after showing intracranial signs a few days after a suspected viral enteritis. Grossly, the right cerebral hemisphere had a large irregular cavity external to the internal capsule. Histopathological examination revealed a cystic lesion in the right hemisphere and non-suppurative inflammation of the diencephalon and periaqueductal nervous tissue. Porencephaly associated with periventricular non-suppurative encephalitis was diagnosed. A nested polymerase chain reaction (PCR) identified the presence of parvovirus DNA in the brain and real-time PCR typed this as canine parvovirus (CPV) type 2a. Immunohistochemistry revealed the presence of CPV antigen in the cytoplasm of scattered cells in the subependymal layers and choroid plexus epithelium. The porencephaly was not associated with inflammatory lesions or CPV antigen and was considered to have preceded the neurological signs. In contrast, the detection of CPV antigen in the subependymal layers and choroid plexus epithelium supported the association of this virus with the periventricular encephalitis.

Glioblastoma: Microenvironment and Niche Concept.

The niche concept was originally developed to describe the location of normal neural stem cells (NSCs) in the subependymal layer of the sub-ventricular zone. In this paper, its significance has been extended to the location of tumor stem cells in glioblastoma (GB) to discuss the relationship between GB stem cells (GSCs) and endothelial cells (ECs). Their interaction is basically conceived as responsible for tumor growth, invasion and recurrence. Niches are described as the points of utmost expression of the tumor microenvironment (TME), therefore including everything in the tumor except for tumor cells: NSCs, reactive astrocytes, ECs, glioma-associated microglia/macrophages (GAMs), myeloid cells, pericytes, fibroblasts, etc. and all intrinsic and extrinsic signaling pathways. Perivascular (PVNs), perinecrotic (PNNs) and invasive niches were described from the pathological point of view, highlighting the basic significance of the EC/tumor stem cell couple. PNN development was reinterpreted based on the concept that hyperproliferative areas of GB are composed of GSCs/progenitors. TME was depicted in its function as the main regulator of everything that happens in the tumor. A particular emphasis was given to GAMs, pericytes and reactive astrocytes as important elements affecting proliferation, growth, invasion and resistance to therapies of tumor cells.

Subcortical neurodegeneration in chorea: Similarities and differences between chorea-acanthocytosis and Huntington's disease

IntroductionChorea-acanthocytosis (ChAc) and Huntington's disease (HD) are neurodegenerative conditions that share clinical and neuropathological features, despite their distinct genetic etiologies. MethodsIn order to compare these neuropathologies, serial gallocyanin-stained brain sections from three subjects with ChAc were analyzed and compared with our previous studies of eight HD cases, in addition to three hemispheres from two male controls. ResultsAstrogliosis was much greater in the ChAc striatum, as compared to that found in HD, with dramatic increase in total striatal glia numbers and the number of glia per striatal neuron. Striatal astrocytes are most likely derived from the striatal subependymal layer in ChAc, which showed massive proliferation. The thalamic centromedian-parafascicular complex is reciprocally connected to the striatum and is more heavily affected in HD than in ChAc. ConclusionThe distinct patterns of selective vulnerability and gliosis observed in HD and ChAc challenge simplistic views on the pathogenesis of these two diseases with rather similar clinical signs. The particular roles played by astroglia in ChAc and in HD clearly need to be elucidated in more detail.

A giant solid cystic inferior fourth ventricle subependymoma – Case report and literature review

Abstract Subependymomas are a rare subtype of ependymomas, slow growing WHO grade I tumors that develop either intracranial from the subependymal glial precursor cells layer of the ventricles or intramedullary. These tumors originate in the undifferentiated Subependymal layer of cells that can become either ependymocytes or astrocytes. Most of the subependymomas are located inside the fourth ventricle (50-60%). We reviewed the case of a 40 years old woman with a giant solid cystic fourth ventricle ependymoma. The patient underwent total resection of the tumor through a subociipital transvermian approach. We discussed the characteristics of these benign tumors and reviewed the literature on this subject and concluded that total resection is the treatment of choice for symptomatic Subependymomas localized in posterior fossa.

Analysis of tuberous sclerosis initially manifested as hypomelanotic macules in 12 infants

Objective To investigate clinical characteristics of tuberous sclerosis (TSC) without nervous system abnormalities in infants. Methods Clinical manifestations of 12 infants with TSC were analyzed. Reflectance confocal microscopy (RCM) was performed in 5 of the 12 infants. Two patients underwent histopathological examination and electron microscopic examination. Results The age at first clinic visit for TSC ranged from 2 to 18 months (median, 8.6 months) among these patients. Before occurrence of nervous symptom, TSC mainly manifested as hypomelanotic macules, nodules in the subependymal layer or walls of lateral ventricles of the brain, cardiac rhabdomyoma and multiple renal cysts. RCM revealed intact dermal papillary rings with low reflectivity and obscure boundaries in 5 infants. Histopathological examination showed a local decrease in melanocytes and pigment granules in basal cells. Electron microscopic examination showed a normal number of melanin granules in the cytoplasm of melanocytes in the basal layer. Conclusions Before appearance of nervous system abnormalities, TSC mainly manifests as hypomelanotic macules in infants, and is easily confused with vitiligo in clinic. RCM examination may serve as a useful method to distinguish infant TSC from hypopigmented diseases. Key words: Tuberous sclerosis; Infant; Hypopigmentation; Vitiligo; Microscopy, confocal

Mimicking Neural Stem Cell Niche by Biocompatible Substrates.

Neural stem cells (NSCs) participate in the maintenance, repair, and regeneration of the central nervous system. During development, the primary NSCs are distributed along the ventricular zone of the neural tube, while, in adults, NSCs are mainly restricted to the subependymal layer of the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus in the hippocampus. The circumscribed areas where the NSCs are located contain the secreted proteins and extracellular matrix components that conform their niche. The interplay among the niche elements and NSCs determines the balance between stemness and differentiation, quiescence, and proliferation. The understanding of niche characteristics and how they regulate NSCs activity is critical to building in vitro models that include the relevant components of the in vivo niche and to developing neuroregenerative approaches that consider the extracellular environment of NSCs. This review aims to examine both the current knowledge on neurogenic niche and how it is being used to develop biocompatible substrates for the in vitro and in vivo mimicking of extracellular NSCs conditions.

The RAGE receptor and its ligands are highly expressed in astrocytes in a grade-dependant manner in the striatum and subependymal layer in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of the CAG repeat in the huntingtin gene. One of the brain changes that occurs in HD is the expression of the receptor for advanced glycation end products (RAGE), a receptor protein capable of activating multiple signalling pathways by interacting with a range of ligands leading to either beneficial or harmful effects to the cell. Here, we demonstrate in human HD brains a high degree of co-localization of RAGE with its putative ligands S100B and N-carboxymethyllysine (CML) in the caudate nucleus (CN) and the subependymal layer (SEL). The level of co-staining for both RAGE-S100B and RAGE-CML was the highest in the astrocytes but was low in neurons and microglia. The immunostaining for RAGE, S100B and CML extended in a medio-lateral (SEL-CN) direction with increasing grade, such that any change in the expression and co-localization pattern between grades was less prominent in the lateral CN. Additionally, signalling molecules that are downstream of RAGE activation showed changes in their activation status in HD brains. A larger number of RAGE-positive astrocytic cells had NF-kB translocated to the nucleus and the level of phospho-ERK1/2 was also increased in HD brains. Interestingly, the level of mDia-1, that interacts directly with the cytoplasmic domain of RAGE, decreased in HD. Overall, the results suggest a correlation between the functions of RAGE and the HD pathology, but the influence of RAGE on astrocytes and the impact of this on HD progression requires further study. RAGE (receptor for advanced glycation end products) binds multiple types of ligand to produce either neurotrophic or neurotoxic effects. Immunohistochemical staining of HD human brains showed that both RAGE and its ligands were expressed primarily in astrocytes. The pattern of staining corresponded to the grade and region-wise pattern of neurodegeneration suggesting a possible role for RAGE in HD pathology.

Olfactory and cortical projections to bulbar and hippocampal adult-born neurons.

New neurons are continually generated in the subependymal layer of the lateral ventricles and the subgranular zone of dentate gyrus during adulthood. In the subventricular zone, neuroblasts migrate a long distance to the olfactory bulb where they differentiate into granule or periglomerular interneurons. In the hippocampus, neuroblasts migrate a short distance from the subgranular zone to the granule cell layer of the dentate gyrus to become granule neurons. In addition to the short-distance inputs, bulbar interneurons receive long-distance centrifugal afferents from olfactory-recipient structures. Similarly, dentate granule cells receive differential inputs from the medial and lateral entorhinal cortices through the perforant pathway. Little is known concerning these new inputs on the adult-born cells. In this work, we have characterized afferent inputs to 21-day old newly-born neurons. Mice were intraperitoneally injected with bromodeoxyuridine. Two weeks later, rhodamine-labeled dextran-amine was injected into the anterior olfactory nucleus, olfactory tubercle, piriform cortex and lateral and medial entorhinal cortices. One week later, animals were perfused and immunofluorescences were carried out. The data show that projection neurons from the mentioned structures, establish putative synaptic contacts onto 21-day-old neurons in the olfactory bulb and dentate gyrus, in some cases even before they start to express specific subpopulation proteins. Long-distance afferents reach middle and outer one-third portions of the molecular layer of the dentate gyrus and granule and, interestingly, periglomerular layers of the olfactory bulb. In the olfactory bulb, these fibers appear to establish presumptive axo-somatic contacts onto newly-born granule and periglomerular cells.

Selective verbal memory impairment due to left fornical crus injury in a patient with intraventricular hemorrhage.

Selective verbal memory impairment due to left fornical crus injury in a patient with intraventricular hemorrhage.

Oculomotor Nerve Injury Induces Nuerogenesis in the Oculomotor and Edinger–Westphal Nucleus of Adult Dog

Technical developments have extensively promoted experimental and clinical studies on cranial nerve regeneration, but intracranial nerve recovery is still an unexplored research area compared to peripheral nerve repair. In this study, we researched whether neurogenesis occurs in adult oculomotor (OMN) and Edinger-Westphal nucleus (EWN) or not after oculomotor nerve injury. To assess cell proliferation in response to unilateral oculomotor nerve crush (ONC) in adult beagle dog, repetitive 5-bromo-2'-deoxyuridine (BrdU) intravenous injections were performed during 3 or 7 days before the dogs were euthanized 2 h after the last injection on days 3, 7, 14, and 28 post-ONC. The proliferating cell types were investigated with three cell phenotypic markers and confocal microscopy on serial sections throughout the whole extent of OMN and EWN. BrdU-positive nuclei were detected in bilateral OMNs and EWNs from 3 to 28 days after ONC with the peak value at 3 days. Confocal analysis revealed that partial BrdU-positive cells colocalized with nestin or βIII-tubulin or GFAP, and the number of every kind of double-labeled cell maintained an increased tendency from 3 to 28 days post-ONC. Neither single-labeled BrdU-positive nuclei nor double-labeled cells were detected in the subependymal layer of cerebral aqueduct (SELCA) of all unilateral ONC dogs; also, they were not observed in the OMNs, EWNs, and SELCA of intact and sham-operated dog. These findings demonstrate that ONC can trigger continual mitotic activity, proliferation of NSCs, neurogenesis, and astrogliogenesis in the OMN and EWN of adult dogs.

Luteinizing hormone-releasing hormone distribution in the anterior hypothalamus of the female rats.

Luteinizing hormone-releasing hormone (LHRH) neurons and fibers are located in the anteroventral hypothalamus, specifically in the preoptic medial area and the organum vasculosum of the lamina terminalis. Most luteinizing hormone-releasing hormone neurons project to the median eminence where they are secreted in the pituitary portal system in order to control the release of gonadotropin. The aim of this study is to provide, using immunohistochemistry and female brain rats, a new description of the luteinizing hormone-releasing hormone fibers and neuron localization in the anterior hypothalamus. The greatest amount of the LHRH immunoreactive material was found in the organum vasculosum of the lamina terminalis that is located around the anterior region of the third ventricle. The intensity of the reaction of LHRH immunoreactive material decreases from cephalic to caudal localization; therefore, the greatest immunoreaction is in the organum vasculosum of the lamina terminalis, followed by the dorsomedial preoptic area, the ventromedial preoptic area, and finally the ventrolateral medial preoptic area, and in fibers surrounding the suprachiasmatic nucleus and subependymal layer on the floor of the third ventricle where the least amount immunoreactive material is found.

From the Radiologic Pathology Archives: Intraventricular Neoplasms: Radiologic-Pathologic Correlation

A variety of neoplasms may arise in the ventricular system. Intraventricular neoplasms may be discovered as an incidental finding at cross-sectional imaging or may manifest with varied symptoms depending on their location, including symptoms of increased intracranial pressure. These lesions may arise from various ventricular structures, including the ependymal lining (eg, ependymoma), subependymal layer (eg, subependymoma), or choroid plexus (eg, choroid plexus neoplasms), or they may have a cell of origin that has yet to be determined (eg, chordoid glioma). Other neoplasms involving the ventricular system include central neurocytoma, subependymal giant cell tumor, meningioma, rosette-forming glioneuronal tumor, and metastases. The differential diagnosis for intraventricular neoplasms can be broad, and many of them have similar patterns of signal intensity and contrast enhancement at imaging. However, the location of the lesion in the ventricular system-along with knowledge of the patient's age, gender, and underlying conditions-will help narrow the differential diagnosis.

Superior medullary velum: anatomical-histological study in the sheep brain and a preliminary tractographic study in the human brain.

To study the anatomy, histology and fiber relations of the superior medullary velum. Ten previously frozen and formalin-fixed sheep brains were used. The fiber dissection was done using the operating microscope at the Rhoton Anatomy Laboratory of Marmara Faculty of Medicine. A tractographic study was conducted on five volunteer patients to see the fiber anatomy of the superior medullary velum. The average thickness and length was found to be 0.296 mm (range 0.09-1 mm) and 4.25 mm (range 3.25-4.5 mm) respectively. Histologically, the superior medullary velum consisted of cuboidal layer of ependymal cells on the anterior surface related to fourth ventricle. The subependymal layer contained hypocellular fibrillary zone with few glial cells, and the outer layer consisted of thin layer of fibroblasts. Under the hypocellular fibrillary zone, abundant axons and organized structures were observed. Tractographically, only a few fibers were identified on diffusion-tensor imaging (DTI). We could not identify a distinct tract anatomically and neuron cells histologically. Neuron-like cells and organized structures were observed on immunohistochemical analysis. Also a few tracts were observed on DTI study as an ascending pathway from spinal tracts to the superior medullary velum. Further studies including human cadaveric, histologic and fiber tractographic investigations are needed to say that it is harmless to divide this anatomical structure.

The relationship between ventricular dilatation, neuropathological and neurobehavioural changes in hydrocephalic rats

BackgroundThe motor and cognitive deficits observed in hydrocephalus are thought to be due to axonal damage within the periventricular white matter. This study was carried out to investigate the relationship between ventricular size, cellular changes in brain, and neurobehavioural deficits in rats with experimental hydrocephalus.MethodsHydrocephalus was induced in three-week old rats by intracisternal injection of kaolin. Behavioural and motor function were tested four weeks after hydrocephalus induction and correlated to ventricular enlargement which was classified into mild, moderate or severe. Gross brain morphology, routine histology and immunohistochemistry for oligodendrocytes (CNPase), microglia (Iba-1) and astrocytes (GFAP) were performed to assess the cellular changes.ResultsDecreases in open field activity and forelimb grip strength in hydrocephalus correlated with the degree of ventriculomegaly. Learning in Morris water maze was significantly impaired in hydrocephalic rats. Gradual stretching of the ependymal layer, thinning of the corpus callosum, extracellular oedema and reduced cortical thickness were observed as the degree of ventriculomegaly increased. A gradual loss of oligodendrocytes in the corpus callosum and cerebral cortex was most marked in the severely-hydrocephalic brains, whereas the widespread astrogliosis especially in the subependymal layer was most marked in the brains with mild hydrocephalus. Retraction of microglial processes and increase in Iba-1 immunoreactivity in the white matter was associated ventriculomegaly.ConclusionsIn hydrocephalic rats, oligodendrocyte loss, microglia activation, astrogliosis in cortical areas and thinning of the corpus callosum were associated with ventriculomegaly. The degree of ventriculomegaly correlated with motor and cognitive deficits.