Chu Min, Hu Xiaoming, Lu Shiduo, Gan Yu, Li Peiying, Guo Yanling, Zhang Jia, Chen Jun, Gao Yanqin
State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Front Biosci (Elite Ed). 2012 Jan 1;4(5):1926-36. doi: 10.2741/513.
Cerebral ischemia triggers regeneration of neural stem/progenitor cells (NSCs/NPCs), which are associated with neovascularization and white matter repair in the brain. This study analyzed the dynamics of neurogenesis, neovascularization, and white matter injury/repair after middle cerebral artery occlusion (MCAO) and elucidated their temporal association. Mice were subjected to MCAO for 60 minutes and sacrificed up to 28 days after reperfusion. Neurogenesis and angiogenesis, as measured by double staining of 5-bromo-2-deoxyuridine (BrdU) with DCX or tomato lectin, respectively, were substantially activated soon after ischemia and persisted for 4 weeks. Despite the moderate recovery of functional vessels in infarct margin from 7 days post-ischemia, a significant decrease in vascular density remained over time. Clusters of immature neurons localized proximal to angiogenic blood vessels beginning 14 days after ischemia, suggesting interplay between neurogenesis and revascularization. Progenitors of oligodendrocytes (NG2+) constitutively presented in the normal brain and proliferated soon after ischemia. However, axon damage and the loss of white matter integrity after ischemic stroke were almost irreversible, as revealed by sustained decreases of myelin basic protein (MBP) and neurofilament-200 expression.
脑缺血会触发神经干细胞/祖细胞（NSCs/NPCs）的再生，这与大脑中的新生血管形成和白质修复有关。本研究分析了大脑中动脉闭塞（MCAO）后神经发生、新生血管形成和白质损伤/修复的动态变化，并阐明了它们的时间关联。将小鼠进行60分钟的MCAO手术，并在再灌注后长达28天处死。分别通过5-溴-2-脱氧尿苷（BrdU）与双皮质素（DCX）或番茄凝集素的双重染色来测量神经发生和血管生成，缺血后很快就会大量激活，并持续4周。尽管缺血后7天梗死边缘的功能性血管有适度恢复，但随着时间的推移，血管密度仍显著下降。缺血14天后，未成熟神经元簇位于血管生成血管的近端，提示神经发生和血管再通之间存在相互作用。少突胶质细胞祖细胞（NG2+）在正常大脑中持续存在，并在缺血后很快增殖。然而，缺血性中风后轴突损伤和白质完整性丧失几乎是不可逆的，髓鞘碱性蛋白（MBP）和神经丝-200表达持续下降表明了这一点。
