Conditional depletion of neurogenesis inhibits long-term recovery after experimental stroke in mice.
We reported previously that ablation of doublecortin (DCX)-immunopositive newborn neurons in mice worsens anatomical and functional outcome measured 1 day after experimental stroke, but whether this effect persists is unknown. We generated transgenic mice that express herpes simplex virus thymidine kinase under control of the DCX promoter (DCX-TK transgenic mice). DCX-expressing and recently divided cells in the rostral subventricular zone (SVZ) and hippocampus of DCX-TK transgenic mice, but not wild-type mice, were specifically depleted after ganciclovir (GCV) treatment for 14 days. Focal cerebral ischemia was induced by permanent distal middle cerebral artery occlusion (MCAO) on day 14 of vehicle or GCV treatment, and mice were killed 12 weeks after MCAO. Infarct volume was significantly increased and neurologic deficits were more severe in GCV- compared to vehicle-treated DCX-TK transgenic mice at first 8 weeks, after depletion of DCX- and bromodeoxyuridine-immunoreactive cells in the SVZ and dentate gyrus following focal ischemia. Our results indicate that endogenous neurogenesis in a critical period following experimental stroke influences the course of long-term recovery.
Buck Institute for Research on Aging, Novato, California, USA.
Xiaomei
X
Wang
XiaoOu
X
Mao
Lin
L
Xie
Fen
F
Sun
David A
DA
Greenberg
Kunlin
K
Jin
D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D015774:Ganciclovir / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology / Q000534:rehabilitation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D020521:Stroke / Q000503:physiopathology*; D000071939:Stroke Rehabilitation
C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D015774:Ganciclovir