Functional ultrastructure of cerebrospinal fluid drainage channels in human arachnoid villi

The functional ultrastructure of the human arachnoid villi was studied to clarify drainage channels of cerebrospinal fluid (CSF). The apical portion of each villus was usually covered by the arachnoid cell layer alone with no endothelial investment, whereas most of the stromal central core was further encompassed by a fibrous capsule with an endothelial investment. Accordingly, the CSF-blood interface was assumed to be in both the endothelial cells and the arachnoid cell layer. The former were characterized by abundant micropinocytotic vesicles and occasional intracytoplasmic vacuoles, whereas the latter was characterized by numerous extracellular cisterns measuring 10 micron in maximal diameter. There were no free communications such as endothelial open junctions or endothelium-lined tubules. In the villi affected by subarachnoid hemorrhage, endothelial cells were intact and continuous despite the erythrocyte-packed subendothelial space, which appeared to be on the verge of rupturing. Intracytoplasmic vacuoles, measuring less than 1 micron diameter, sometimes contained serum protein-like substance. Furthermore, the extracellular cisterns were distended by intact or disintegrating erythrocytes that served as a natural tracer, suggesting CSF drainage channels. It is conceivable that, in human arachnoid villi, the extracellular cisterns of the arachnoid cell layer contribute to the passive transport of CSF, whereas micropinocytosis and vacuolization mechanisms of the endothelial cells are available for active transport.     

Repetitive intratumoral hemorrhage in medulloblastoma: A case report

An 8-year-old girl experienced five repeated hemorrhagic episodes around the cerebellar vermis. Surgical specimens histologically showed abnormal vascular components invaded by tumor cells. Autopsy disclosed medulloblastoma disseminating in the subependymal zone of the ventricles. An atypical clinical course is reported with special attention to the cause of hemorrhage.     

Congenital multiple cavernous angiomas associated with thrombosed arteriovenous malformation of the brain--case report

A 16-year-old girl presented with multiple cerebral cavernous angiomas with calcifications due to repeated hemorrhages and a thrombosed cerebral arteriovenous malformation (AVM). Her 18-year-old elder sister also had multiple cerebral cavernous angiomas associated with calcifications, which suggested presence of repeated previous hemorrhages. Surgical removal via a right occipital craniotomy resulted in a good outcome. The histological diagnosis was thrombosed AVM. Evaluation of congenital vascular anomaly needs to take into consideration the combination of other congenital vascular anomalies and their familial occurrence.     

Expression of the endoplasmic reticulum molecular chaperone (ORP150) rescues hippocampal neurons from glutamate toxicity

A series of events initiated by glutamate-receptor interaction perturbs cellular homeostasis resulting in elevation of intracellular free calcium and cell death. Cells subject to such environmental change express stress proteins, which contribute importantly to maintenance of metabolic homeostasis and viability. We show that an inducible chaperone present in endoplasmic reticulum (ER), the 150-kDa oxygen-regulated protein (ORP150), is expressed both in the human brain after seizure attack and in mouse hippocampus after kainate administration. Using mice heterozygous for ORP150 deficiency, exposure to excitatory stimuli caused hippocampal neurons to display exaggerated elevation of cytosolic calcium accompanied by activation of mu-calpain and cathepsin B, as well as increased vulnerability to glutamate-induced cell death in vitro and decreased survival to kainate in vivo. In contrast, targeted neuronal overexpression of ORP150 suppressed each of these events and enhanced neuronal and animal survival in parallel with diminished seizure intensity. Studies using cultured hippocampal neurons showed that ORP150 regulates cytosolic free calcium and activation of proteolytic pathways causing cell death in neurons subject to excitatory stress. Our data underscore a possible role for ER stress in glutamate toxicity and pinpoint a key ER chaperone, ORP150, which contributes to the stress response critical for neuronal survival.