Conditional depletion of neurogenesis inhibits long-term recovery after experimental stroke in mice

Xiaomei Wang, Xiao Ou Mao, Lin Xie, Fen Sun, David A. Greenberg, Kunlin Jin

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere38932
JournalPLoS ONE
Volume7
Issue number6
DOIs
StatePublished - 19 Jun 2012

Fingerprint

Ganciclovir
neurogenesis
Neurogenesis
stroke
Transgenic Mice
Stroke
Recovery
Lateral Ventricles
Middle Cerebral Artery Infarction
mice
genetically modified organisms
Thymidine Kinase
Bromodeoxyuridine
Ablation
Viruses
Neurons
ischemia
Dentate Gyrus
arteries
Simplexvirus

Cite this

Wang, Xiaomei ; Mao, Xiao Ou ; Xie, Lin ; Sun, Fen ; Greenberg, David A. ; Jin, Kunlin. / Conditional depletion of neurogenesis inhibits long-term recovery after experimental stroke in mice. In: PLoS ONE. 2012 ; Vol. 7, No. 6.
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Conditional depletion of neurogenesis inhibits long-term recovery after experimental stroke in mice. / Wang, Xiaomei; Mao, Xiao Ou; Xie, Lin; Sun, Fen; Greenberg, David A.; Jin, Kunlin.

In: PLoS ONE, Vol. 7, No. 6, e38932, 19.06.2012.

Research output: Contribution to journalArticle

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