Estrogen enhances neurogenesis and behavioral recovery after stroke

Stroke is a leading cause of permanent disability and death. It is well accepted that the principal mammalian estrogen (E2), 17-beta estradiol, provides robust neuroprotection in a variety of brain injury models in animals of both sexes. E2 enhances neurogenesis after stroke in the subventricular zone; however, it is unknown if these cells survive long-term or enhance functional recovery. In this study, we examined stroke-induced neurogenesis in male, gonadally intact female, and ovariectomized female mice 2 and 6 weeks after stroke. Treatment with 17-beta estradiol increased 5-bromo-2'-deoxyuridine-labeled cells at both time points in both the dentate gyrus and subventricular zone; the majority were colabeled with doublecortin at 2 weeks and with NeuN at 6 weeks. Stroke-induced neurogenesis was reduced in estrogen receptor knockout mice, as well as in mice lacking the gene for aromatase, which converts testosterone into E2. Improved behavioral deficits were seen in E2-treated mice, suggesting that E2-induced increases in poststroke neurogenesis contribute to poststroke recovery. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 413-425; doi: 10.1038/jcbfm.2010.181; published online 13 October 2010