Bilateral cerebellar epithelioid hemangioblastoma with possible ependymal differentiation in a patient with von Hippel–Lindau disease

There are controversies regarding the histogenesis of stromal cells of hemangioblastoma, and no hypothesis has conclusively been proven. We report a case of unusual hemangioblastoma in a middle‐aged man with von Hippel‐Lindau disease. Neuroimaging revealed multifocal gadolinium‐enhancing masses were located within both sides of the cerebellar hemisphere. Histologically, only small areas showing the typical morphology of hemangioblastoma were recognized in masses. Most areas of masses were composed of cohesive epithelioid tumor cells with abundant cytoplasm and distinct boundaries. Epithelioid tumor cells were arranged around blood vessels, exhibiting perivascular anuclear zone structures like ependymoma. The epithelioid tumor cells were diffusely positive for vimentin, CD99, neuron‐specific enolase, GFAP and focally positive for epithelial membrane antigen (EMA) and D2‐40 in a dot‐like pattern. Variable‐sized lipid droplets and glycogen particles were noted in the cytoplasm of epithelioid tumor cells under an electron microscope. A diagnosis of epithelioid cellular hemangioblastoma with possible ependymal differentiation (WHO grade I) was made. To our knowledge, only a few cases of hemangioblastoma show epithelioid appearance or EMA immunoreactivity. The present case indicates that the stromal cells of hemangioblastoma might originate from primitive neuroectodermal cells, and they have the capacity to show a distinctive sign of glial or ependymal differentiation.     

Dysregulation of Kruppel-like factor 4 during brain development leads to hydrocephalus in mice

Kruppel-like factor 4 (KLF4) is involved in self-renewal of embryonic stem cells and reprogramming of somatic cells to pluripotency. However, its role in lineage-committed stem cells remains largely unknown. Here, we show that KLF4 is expressed in neural stem cells (NSCs) and is down-regulated during neuronal differentiation. Unexpectedly, enhanced expression of KLF4 reduces self-renewal of cultured NSCs and inhibits proliferation of subventricular neural precursors in transgenic mice. Mice with increased KLF4 in NSCs and NSCs-derived ependymal cells developed hydrocephalus-like characteristics, including enlarged ventricles, thinned cortex, agenesis of the corpus callosum, and significantly reduced subcommissural organ. These characteristics were accompanied by elevation of GFAP expression and astrocyte hypertrophy. The ventricular cilia, vital for cerebrospinal fluid flow, are also disrupted in the mutant mice. These results indicate that down-regulation of KLF4 is critical for neural development and its dysregulation may lead to hydrocephalus.     

Cervical intradural extramedullary ependymal cyst associated with congenital dermal sinus: a case report

Spinal intradural extramedullary ependymal cyst is a very rare entity with only few cases reported in the literature. Its association with congenital dermal sinus has not been described so far. We present a unique report of a 3-year-old male child who presented with spastic quadriparesis with a trophic ulcer in the right great toe of 1-year duration. He harbored a congenital dermal sinus in the cervical spine since birth. Intraoperatively, the sinus was associated with an intradural cyst which proved to be an ependymal cyst on histopathological examination. The clinical profile along with review of literature of this rare entity is presented.     

大鼠脊髓损伤后室管膜细胞增殖迁移及可塑性研究

[目的]研究大鼠脊髓损伤后室管膜细胞的原位增殖、迁移及其可塑性。[方法]Wistar大鼠60只，制作大鼠脊髓全横断损伤模型，根据伤后不同时间点分组，应用免疫组织化学方法动态检测脊髓内5-溴脱氧尿嘧啶（Brdu）、多唾液酸神经细胞黏附分子（PSA—NCAM）的表达。[结果]与对照组相比，Brdu阳性细胞在脊髓损伤后1d开始增加（P〈0．05），7d达到高峰，14d后开始下降，但仍高于对照组（P〈0．05）；PSA—NCAM阳性细胞在脊髓损伤后3d开始增加（P〈0．05），7d达到高峰，14d后开始下降，但仍高于对照组（P〈0．05）；两者在时间上均呈一过性增高表达，空间上自中心向周围迁移。[结论]脊髓损伤可激活自体室管膜细胞的原位增殖及迁移．后者具有一定的可甥性．参与伤后脊髓的结构修复。     

The adult spinal cord harbors a population of GFAP‐positive progenitors with limited self‐renewal potential

Adult neural stem cells (aNSCs) of the forebrain are GFAP‐expressing cells that are intercalated within ependymal cells of the subventricular zone (SVZ). Cells showing NSCs characteristics in vitro can also be isolated from the periaqueductal region in the adult spinal cord (SC), but contradicting results exist concerning their glial versus ependymal identity. We used an inducible transgenic mouse line (hGFAP‐CreERT2) to conditionally label GFAP‐expressing cells in the adult SVZ and SC periaqueduct, and directly and systematically compared their self‐renewal and multipotential properties in vitro. We demonstrate that a population of GFAP⁺ cells that share the morphology and the antigenic properties of SVZ‐NSCs mostly reside in the dorsal aspect of the central canal (CC) throughout the spinal cord. These cells are non‐proliferative in the intact spinal cord, but incorporate the S‐phase marker EdU following spinal cord injury. Multipotent, clonal YFP‐expressing neurospheres (i.e., deriving from recombined GFAP‐expressing cells) were successfully obtained from both the intact and injured spinal cord. These spheres however showed limited self‐renewal properties when compared with SVZ‐neurospheres, even after spinal cord injury. Altogether, these results demonstrate that significant differences exist in NSCs lineages between neurogenic and non‐neurogenic regions of the adult CNS. Thus, although we confirm that a population of multipotent GFAP⁺ cells co‐exists alongside with multipotent ependymal cells within the adult SC, we identify these cells as multipotent progenitors showing limited self‐renewal properties. GLIA 2013;61:2100–2113     

Sodium vitamin C cotransporter SVCT2 is expressed in hypothalamic glial cells

Kinetic analysis of vitamin C uptake demonstrated that different specialized cells take up ascorbic acid through sodium-vitamin C cotransporters. Recently, two different isoforms of sodium-vitamin C cotransporters (SVCT1/SLC23A1 and SVCT2/SLC23A2) have been cloned. SVCT2 was detected mainly in choroidal plexus cells and neurons; however, there is no evidence of SVCT2 expression in glial and endothelial cells of the brain. Certain brain locations, including the hippocampus and hypothalamus, consistently show higher ascorbic acid values compared with other structures within the central nervous system. However, molecular and kinetic analysis addressing the expression of SVCT transporters in cells isolated from these specific areas of the brain had not been done. The hypothalamic glial cells, or tanycytes, are specialized ependymal cells that bridge the cerebrospinal fluid with different neurons of the region. Our hypothesis postulates that SVCT2 is expressed selectively in tanycytes, where it is involved in the uptake of the reduced form of vitamin C (ascorbic acid), thereby concentrating this vitamin in the hypothalamic area. In situ hybridization and optic and ultrastructural immunocytochemistry showed that the transporter SVCT2 is highly expressed in the apical membranes of mouse hypothalamic tanycytes. A newly developed primary culture of mouse hypothalamic tanycytes was used to confirm the expression and function of the SVCT2 isoform in these cells. The results demonstrate that tanycytes express a high-affinity transporter for vitamin C. Thus, the vitamin C uptake mechanisms present in the hypothalamic glial cells may perform a neuroprotective role concentrating vitamin C in this specific area of the brain.     

Rat neural antigen-2 (RAN-2): A cell surface antigen on astrocytes, ependymal cells, Müller cells and lepto-meninges defined by a monoclonal antibody

We have immunized mice with enriched populations of cultured rat astrocytes and fused their spleen cells with NS-1 myeloma cells to generate antibody-secreting hybridomas. We have isolated two stable hybridoma clones which secrete monoclonal IgG₂ antibodies that react with the surface of the great majority of rat astrocytes in culture. We have studied one of these antibodies in indirect immunofluorescence assays and show that it binds to the surface of rat ependymal cells, retinal Müller cells and leptomeningeal cells as well as to astrocytes, but not to cultured neurones, oligodendrocytes, Schwann cells, microglia or various non-neural cells. The antigen defined by this monoclonal antibody is protease-sensitive and rat-specific and we have called it rat neural antigen-2 (Ran-2).We also show that isolated rat ependymal cells and cultured rat Müller cells do not express other neural cell-type-specific markers, such as tetanus toxin receptors, rat neural antigen-1 (Ran-1), galactocerebroside or glial fibrillary acidic protein (GFAP). Nor do these cells express cell surface Fc receptors for IgG, phagocytose latex beads or make detectable amounts of the Thy-1 or fibronectin glycoproteins.