Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, WuLuMuQi Middle Road 12, Shanghai, 200040, China.
State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200040, China.
Transl Stroke Res. 2019 Apr;10(2):150-159. doi: 10.1007/s12975-018-0629-8. Epub 2018 Apr 26.
Brain has limited capacity for spontaneous recovery of lost function after stroke. Exposure to enriched environment (EE) can facilitate functional recovery, but mechanisms underlying this effect are poorly understood. Here, we used a middle cerebral artery occlusion (MCAO) model to investigate the impact of EE on angiogenesis in the post-ischemic brain in adult male Sprague Dawley rats, and examined whether blood-borne factors may contribute. Compared with standard cage (SC), exposure to EE was associated with greater improvement in neurological function, higher peri-infarct vascular density, and higher chronic post-ischemic cerebral blood flow assessed by laser speckle imaging. The effect persisted for at least 28 days. EE also enhanced the expression of hepatocyte growth factor in the peri-ischemic cortex when measured 15 days after MCAO. Interestingly, serum from rats exposed to EE after MCAO showed elevated levels of hepatocyte growth factor, and plasma or serum from rats exposed to EE after MCAO enhanced the survival and proliferation of cultured endothelial cells, in vitro, when compared with control plasma or serum from SC group after MCAO. Together, our data suggest that exposure to EE promotes angiogenesis in the ischemic brain that may in part be mediated by blood-borne factors.
大脑在中风后丧失功能后,其自身恢复的能力是有限的。置身于丰富环境(EE)中可以促进功能恢复,但这种效果的机制尚不清楚。在这里,我们使用大脑中动脉闭塞(MCAO)模型来研究 EE 对成年雄性 Sprague Dawley 大鼠缺血后大脑血管生成的影响,并探讨了血液传播因素是否可能起到作用。与标准笼(SC)相比,EE 暴露与神经功能的改善、梗死周围血管密度的增加以及激光散斑成像评估的慢性缺血后脑血流的增加有关。这种效果至少持续 28 天。EE 还增强了 MCAO 后 15 天缺血皮质周围肝细胞生长因子的表达。有趣的是,MCAO 后暴露于 EE 的大鼠的血清中肝细胞生长因子水平升高,而 MCAO 后暴露于 EE 的大鼠的血浆或血清在体外可增强培养的内皮细胞的存活和增殖,与 MCAO 后 SC 组的对照血浆或血清相比。总之,我们的数据表明,EE 暴露可促进缺血性大脑中的血管生成,这可能部分是由血液传播因素介导的。