Abstract
The unique cellular and vascular architecture of the adult ventricular-subventricular zone (V/SVZ) neurogenic niche plays an important role in regulating neural stem cell function. However, the in vivo identification of neural stem cells and their relationship to blood vessels within this niche in response to stroke remain largely unknown. Using whole-mount preparation of the lateral ventricle wall, we examined the architecture of neural stem cells and blood vessels in the V/SVZ of adult mouse over the course of 3 months after onset of focal cerebral ischemia. Stroke substantially increased the number of glial fibrillary acidic protein (GFAP) positive neural stem cells that are in contact with the cerebrospinal fluid (CSF) via their apical processes at the center of pinwheel structures formed by ependymal cells residing in the lateral ventricle. Long basal processes of these cells extended to blood vessels beneath the ependymal layer. Moreover, stroke increased V/SVZ endothelial cell proliferation from 2% in non-ischemic mice to 12 and 15% at 7 and 14 days after stroke, respectively. Vascular volume in the V/SVZ was augmented from 3% of the total volume prior to stroke to 6% at 90 days after stroke. Stroke-increased angiogenesis was closely associated with neuroblasts that expanded to nearly encompass the entire lateral ventricular wall in the V/SVZ. These data indicate that stroke induces long-term alterations of the neural stem cell and vascular architecture of the adult V/SVZ neurogenic niche. These post-stroke structural changes may provide insight into neural stem cell mediation of stroke-induced neurogenesis through the interaction of neural stem cells with proteins in the CSF and their sub-ependymal neurovascular interaction.
Highlights
The ventricular-subventricular zone (V/SVZ) of the lateral ventricles in adult rodent brain is a neurogenic niche which contains neural stem cells that generate intermediate neural progenitor cells
We found that whole-mounts from mice subjected to 30 days of MCA occlusion (MCAO) showed an increase in the number of single c-tubulin+ basal body with single short acetylated tubulin+ cilium and the number of glial fibrillary acidic protein (GFAP)+ cells with single c-tubulin+ basal body on the ventricular wall (Fig. 1A–F))
Stroke induced-neurogenesis has been demonstrated in experimental animals and human patients [5,6,7]; there is no direct in vivo evidence showing the effect of stroke on neural stem cells and their relationship with blood vessels in the V/SVZ of the adult rodent
Summary
The ventricular-subventricular zone (V/SVZ) of the lateral ventricles in adult rodent brain is a neurogenic niche which contains neural stem cells that generate intermediate neural progenitor cells. These intermediate neural progenitor cells, in turn, differentiate into olfactory bulb interneurons throughout animal’s life [1,2,3,4]. Stroke increases neurogenesis and newly generated neuroblasts in the V/SVZ migrate to the ischemic boundary region [5,6,7]. Due to technical challenges of identifying neural stem cells in the V/SVZ there is no direct in vivo evidence demonstrating the effect of stroke on neural stem cells
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