Li Jun, Siegel Matt, Yuan Mike, Zeng Zhiyuan, Finnucan Laura, Persky Rebecca, Hurn Patricia D, McCullough Louise D
Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
J Cereb Blood Flow Metab. 2011 Feb;31(2):413-25. doi: 10.1038/jcbfm.2010.181. Epub 2010 Oct 13.
Stroke is a leading cause of permanent disability and death. It is well accepted that the principal mammalian estrogen (E2), 17-β 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-β 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.
中风是导致永久性残疾和死亡的主要原因。人们普遍认为，主要的哺乳动物雌激素（E2），即17-β雌二醇，在各种性别动物的脑损伤模型中都能提供强大的神经保护作用。E2可增强中风后脑室下区的神经发生；然而，这些细胞是否能长期存活或促进功能恢复尚不清楚。在本研究中，我们在中风后2周和6周检查了雄性、性腺完整的雌性和去卵巢雌性小鼠中风诱导的神经发生情况。在齿状回和脑室下区的两个时间点，用17-β雌二醇治疗均增加了5-溴-2'-脱氧尿苷标记的细胞；大多数细胞在2周时与双皮质素共标记，在6周时与NeuN共标记。雌激素受体基因敲除小鼠以及缺乏将睾酮转化为E2的芳香化酶基因的小鼠中，中风诱导的神经发生减少。在E2治疗的小鼠中观察到行为缺陷改善，这表明E2诱导的中风后神经发生增加有助于中风后恢复。
