title: Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct boundary in adult rats.
abstract: Stroke increases neurogenesis. The authors investigated whether neural stem cells or progenitor cells in the adult subventricular zone (SVZ) of rats contribute to stroke-induced increase in neurogenesis. After induction of stroke in rats, the numbers of cells immunoreactive to doublecortin, a marker for immature neurons, increased in the ipsilateral SVZ and striatum. Infusion of an antimitotic agent (cytosine-beta-D-arabiofuranoside, Ara-C) onto the ipsilateral cortex eliminated more than 98% of actively proliferating cells in the SVZ and doublecortin-positive cells in the ipsilateral striatum. However, doublecortin-positive cells rapidly replenished after antimitotic agent depletion of actively proliferating cells. Depleting the numbers of actively proliferating cells in vivo had no effect on the numbers of neurospheres formed in vitro, yet the numbers of neurospheres derived from stroke rats significantly (P<0.05) increased. Neurospheres derived from stroke rats self-renewed and differentiated into neurons and glia. In addition, doublecortin-positive cells generated in the SVZ migrated in a chainlike structure toward ischemic striatum. These findings indicate that in the adult stroke brain, increases in recruitment of neural stem cells contribute to stroke-induced neurogenesis, and that newly generated neurons migrate from the SVZ to the ischemic striatum.
authors.affiliation: Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
authors.forename: Ruilan
authors.initials: R
authors.lastname: Zhang
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Anton
authors.initials: A
authors.lastname: Gousev
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Khang-Loon
authors.initials: KL
authors.lastname: Ho
authors.forename: Cindi
authors.initials: C
authors.lastname: Morshead
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D020768:Middle Cerebral Artery / Q000473:pathology; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000502:physiology* / Q000648:ultrastructure
chemical_list: C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D003561:Cytarabine