Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct boundary in adult rats.
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.
Zhang
Ruilan
R
Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
Zhang
Zhenggang
Z
Wang
Lei
L
Wang
Ying
Y
Gousev
Anton
A
Zhang
Li
L
Ho
Khang-Loon
KL
Morshead
Cindi
C
Chopp
Michael
M
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
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D003561:Cytarabine