The development of a cerebral organoid culture in vitro offers an opportunity to generate human brain-like organs to investigate mechanisms of human disease that are specific to the neurogenesis of radial glial (RG) and outer radial glial (oRG) cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing neocortex. Modeling neuronal progenitors and the organization that produces mature subcortical neuron subtypes during early stages of development is essential for studying human brain developmental diseases. Several previous efforts have shown to grow neural organoid in culture dishes successfully, however we demonstrate a new paradigm that recapitulates neocortical development process with VZ, OSVZ formation and the lamination organization of cortical layer structure. In addition, using patient-specific induced pluripotent stem cells (iPSCs) with dysfunction of the Aspm gene from a primary microcephaly patient, we demonstrate neurogenesis defects result in defective neuronal activity in patient organoids, suggesting a new strategy to study human developmental diseases in central nerve system.
Action Potentials ; physiology ; Biomarkers ; metabolism ; Cell Culture Techniques ; Embryoid Bodies ; cytology ; metabolism ; Gene Expression ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Lateral Ventricles ; cytology ; growth & development ; metabolism ; Microcephaly ; genetics ; metabolism ; pathology ; Models, Biological ; Mutation ; Neocortex ; cytology ; growth & development ; metabolism ; Nerve Tissue Proteins ; deficiency ; genetics ; Neurogenesis ; genetics ; Neurons ; cytology ; metabolism ; Organoids ; cytology ; metabolism ; PAX6 Transcription Factor ; genetics ; metabolism ; Patch-Clamp Techniques ; SOXB1 Transcription Factors ; genetics ; metabolism ; Zonula Occludens-1 Protein ; genetics ; metabolism

OBJECTIVETo observe the time course of proliferation and differentiation of neural stem cells (NSCs) in the subventricular zone (SVZ) of rats following traumatic craniocerebral injury (TBI).

METHODSForty-eight SD rats were randomized into 3 groups, namely the control group without any treatment, the sham-operated group with scalp incision and preparation of a cranial window, and TBI group with craniocerebral injury induced by Feeney's method. With nestin and BrdU as two cell markers, NSE as the neuron-specific marker and GFAP as the glial cell marker, immunofluorescence assay with double labeled antibodies was performed to examine the proliferation and differentiation of endogenous NSCs in the SVZ at different time points after TBI.

RESULTSs The numbers of cells positive for nestin/NSE, nestin/GFAP, BrdU/NSE, and BrdU/GFAP in the SVZ of the rats increased significantly after TBI. The positive cells began to increase at 1 day after TBI, reached the peak level at day 3 and became normal at day 14, showing significant differences between the time points of measurement following TBI and from the cell numbers in the control group measured at the same time points. The cells positive for nestin/ GFAP showed the most distinct increase in the SVZ of the rats with TBI.

CONCLUSIONTBI results in mobilization of the NSCs in the SVZ on the injured side to cause the proliferation and differentiation of the endogenous NSCs. The SVZ is one of the most important germinal centers of NSC proliferation and differentiation.

Animals ; Bromodeoxyuridine ; metabolism ; Cell Differentiation ; Cell Proliferation ; Craniocerebral Trauma ; pathology ; Glial Fibrillary Acidic Protein ; metabolism ; Lateral Ventricles ; cytology ; Nestin ; metabolism ; Neural Stem Cells ; cytology ; Neuroglia ; cytology ; Neurons ; cytology ; Phosphopyruvate Hydratase ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Chordoid glioma is a rare low grade tumor typically located in the third ventricle. Although a chordoid glioma can arise from ventricle with tumor cells having features of ependymal differentiation, intraventricular dissemination has not been reported. Here we report a case of a patient with third ventricular chordoid glioma and intraventricular dissemination in the lateral and fourth ventricles. We described the perfusion MR imaging features of our case different from a previous report.
Adult ; Cerebral Ventricle Neoplasms/diagnosis/pathology/*secondary ; Fourth Ventricle/*pathology ; Glioma/diagnosis/*pathology ; Humans ; Lateral Ventricles/*pathology ; Magnetic Resonance Imaging/methods ; Male ; Third Ventricle/*pathology

Lateral ventricular meningiomas (LVMs) are especially rare, and they often remain "silent" until they become very large. Several surgical approaches exist, but the optimal surgical strategy for them remains a challenge. The incidence, clinical features, radiological manifestations, pathological findings, and especially the surgical strategy in 21 patients with LVMs were analyzed retrospectively. The mean age of patients was 42.7 years (range, 17 to 78 years). Raised intracranial pressure was the main presenting symptom. The definite diagnosis of LVMs in most cases was made by computed tomography (CT) or magnetic resonance imaging (MRI). Six patients were subjected to plain CT scans, 15 to contrast MR scans, and 4 to a magnetic resonance angiogram (MRA). Large tumors were seen in most cases with an average diameter of more than 4.3 cm. Of the 21 cases of LVMs in our series, LVMs were resected in 16 cases via a posterior parieto-occipital transcortical approach, 2 cases via a transcallosal approach, and 3 cases via a posterior middle temporal gyrus approach. In 8 out of 21 cases, the tumors were located in the left lateral ventricle. The gross total surgical excision was achieved in 18 (86%) patients, and all LVMs were pathologically confirmed to be benign. Nine patients were followed up (range: 11 months-4.6 years). Eight (88.9%) cases obtained good recovery and one (11.1%) obtained moderate disability. Four approaches are available for the surgical treatment of LVMs. The choice of surgical approaches depends on tumor location, laterality, size and extension, and the function of the brain must be taken into account. Intracapsular resection and piecemeal resection of LVMs can be safely and easily performed. Preoperative MRA scan is important to know the feeder of LVMs and peripheral blood supply.
Adolescent ; Adult ; Aged ; Female ; Humans ; Intracranial Hypertension ; diagnosis ; pathology ; surgery ; Lateral Ventricles ; blood supply ; pathology ; surgery ; Magnetic Resonance Imaging ; Male ; Meningeal Neoplasms ; blood supply ; diagnosis ; pathology ; surgery ; Meningioma ; blood supply ; diagnosis ; pathology ; surgery ; Middle Aged ; Neurosurgical Procedures ; Retrospective Studies ; Tomography, X-Ray Computed ; Tumor Burden

The purpose of this study is to explore the fate and effect of human embryonic neural stem cells (hNSCs) after transplantation into ipsilateral lateral ventricle of stroke rats. Adult rats were exposed to one-hour transient middle cerebral artery occlusion (MCAO), and then hNSCs were transplanted into ipsilateral lateral ventricle 7 days after reperfusion. Infarct volume was calculated by cresyl violet staining. The improvements of neural functions were assessed by behavioral tests. Immunofluorescence staining was performed to observe the migration and differentiation of transplanted hNSCs. The results showed that transplanted hNSCs significantly reduced ischemia-induced infarction in MCAO rats, and improved neural functional restoration when assessed by rotarod, footfault and corner-turn tests. The grafted cells migrated predominantly to several specific brain regions, such as corpus callosum and peri-infarct area. Furthermore, these cells differentiated into oligodendrocytes and astrocytes in corpus callosum, and neurons in peri-infarct parenchyma. These results suggest that transplanted hNSCs through lateral ventricle of the ischemic side may exert effective therapeutic effects on stroke rats via migration and differentiation in specific brain regions.
Animals ; Astrocytes ; cytology ; Brain ; cytology ; pathology ; Cell Differentiation ; Cell Movement ; Humans ; Infarction, Middle Cerebral Artery ; therapy ; Lateral Ventricles ; Neural Stem Cells ; transplantation ; Neurons ; cytology ; Oligodendroglia ; cytology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the etiology, pathogenesis, clinicopathologic characteristics, clinical prognosis and treatment of Dandy-Walker syndrome.

METHODSNine cases of Dandy-Walker syndrome were included in the study. The autopsy findings and clinical history were evaluated along with review of the literature. The causes, pathogenetic mechanism, pathologic features and prognosis of Dandy-Walker syndrome were analyzed.

RESULTSAmong 9 Dandy-Walker syndrome cases, six patients presented with variants of Dandy-Walker complex and 3 cases had classic Dandy-Walker malformation. In addition, 4 patients presented with combined lateral ventricle expansion and multiple malformations were seen in 7 cases. Combined umbilical cord abnormality was noted in 4 patients with variant of Dandy-Walker complex and combined placental abnormality was seen in one classic Dandy-Walker syndrome.

CONCLUSIONSDandy-Walker syndrome is a rare disease. In addition to complex pathogenesis with possible genetic and environmental antigenic etiologies, placental and umbilical cord abnormality may be also related to its development.

Abortion, Induced ; Autopsy ; Dandy-Walker Syndrome ; diagnostic imaging ; pathology ; Female ; Fetal Diseases ; diagnostic imaging ; pathology ; Fetus ; pathology ; Gestational Age ; Humans ; Lateral Ventricles ; pathology ; Male ; Placental Insufficiency ; pathology ; Pregnancy ; Retrospective Studies ; Ultrasonography, Prenatal

OBJECTIVETo observe the effect of intracerebroventricular injection of rAAV-HIF-1α on hippocampal neuronal apoptosis in a rat model of Alzheimer disease (AD).

METHODSThirty-two male SD rats (250-300 g) were randomized into 4 groups (n=8), including the normal control group without any treatment, AD model group with right intracerebroventricular injection of 2 µl Aβ25-35 (10 mg/m1), sham-operated group with right intracerebroventricular injection of 2 µl normal saline, and AD+ rAAV-HIF-1α group with right intracerebroventricular injection of 10 µl rAAV-HIF-1a (1×10¹² v.g./m1) one week after Aβ25-35 injection. The rats were sacrificed to detect the expression of HIF-1α and apoptosis of hippocampal neurons 5 weeks after Aβ25-35 or saline injection.

RESULTSWestern blotting showed that the expression of HIF-1α was significantly higher in AD+rAAV-HIF-1α group (451.59±34.39) than in normal control group (229.05±41.28) and sham-operated group (216.29±37.08) (P<0.05) without significant difference between the latter two groups. The apoptotic ratio of the hippocampal neurons was significantly higher in AD model group ([19.49±2.59]%) than in normal control group ([5.41±0.75]%) and sham-operated group ([5.28±0.66]%) in (P<0.05), and intracerebroventricular injection of rAAV-HIF-1α resulted in a significant reduction of the apoptotic ratio in the AD rats ([12.07±2.06]%) (P<0.05).

CONCLUSIONIntracerebroventricular injection of rAAV-HIF-1α can inhibit hippocampal neuronal apoptosis in the rat model of AD.

Alzheimer Disease ; metabolism ; therapy ; Animals ; Apoptosis ; Disease Models, Animal ; Hippocampus ; cytology ; Hypoxia-Inducible Factor 1, alpha Subunit ; administration & dosage ; genetics ; metabolism ; Lateral Ventricles ; Male ; Neurons ; drug effects ; pathology ; Rats ; Rats, Sprague-Dawley

Choroid Plexus Neoplasms ; pathology ; Female ; Humans ; Infant ; Lateral Ventricles ; pathology

Adult ; Humans ; Lateral Ventricles ; pathology ; Male ; Neurocytoma ; pathology

Adult ; Cerebral Ventricle Neoplasms ; diagnosis ; metabolism ; Diagnosis, Differential ; Glial Fibrillary Acidic Protein ; analysis ; Humans ; Immunohistochemistry ; Lateral Ventricles ; chemistry ; pathology ; Male