title: Stroke increases neural stem cells and angiogenesis in the neurogenic niche of the adult mouse.
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.
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, United States of America.
authors.forename: Rui Lan
authors.initials: RL
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, United States of America; Department of Physics, Oakland University, Rochester, Michigan, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, United States of America.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Roberts
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, United States of America.
authors.forename: Xianshuang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, United States of America.
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, United States of America.
authors.forename: Siamak P
authors.initials: SP
authors.lastname: Nejad-Davarani
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, United States of America.
authors.forename: Xinli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Michigan, United States of America.
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply*; D002545:Brain Ischemia / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology; D005904:Glial Fibrillary Acidic Protein; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis; D020521:Stroke / Q000209:etiology / Q000473:pathology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C528900:glial fibrillary astrocytic protein, mouse