Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai 200041, China.
Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Neural Plast. 2020 Nov 12;2020:8840319. doi: 10.1155/2020/8840319. eCollection 2020.
An enriched environment (EE) has been demonstrated to improve functional recovery in animal models of ischaemic stroke through enhancing vascular endothelial growth factor- (VEGF-) mediated neuroprotection accompanied by angiogenesis in the ischaemic hemisphere. Whether EEs also promote VEGF-mediated neuroprotection and angiogenesis in the contralateral hemisphere remains unclear. Here, we explored the effect of EEs on VEGF expression and angiogenesis within the contralateral cerebral cortex in a rat middle cerebral artery occlusion/reperfusion (MCAO/r) model. We assessed the expression levels of platelet endothelial cell adhesion molecule-1 (CD31), VEGF, and endothelial nitric oxide synthase (eNOS) in the whole contralateral cerebral cortex using Western blotting assay but did not find an increase in the expression of CD31, VEGF, or eNOS in MCAO/r rats housed in EEs, which suggested that EEs did not enhance the overall expression of VEGF and eNOS or angiogenesis in the entire contralateral cortex. We further analysed the local effect of EEs by immunohistochemistry and found that in and around the bilateral cingulum in MCAO/r rats housed in EEs, haematopoietic progenitor cell antigen- (CD34-) positive endothelial progenitor cells were significantly increased compared with those of rats housed in standard cages (SCs). Further experiments showed that EEs increased neuronal VEGF expression surrounding the cingulum in MCAO/r rats and robustly upregulated eNOS expression. These results revealed that EEs enhanced angiogenesis, VEGF expression, and activation of the VEGF-eNOS pathway in and/or around the cingulum in MCAO/r rats, which were involved in the functional recovery of MCAO/r rats.
丰富环境（EE）已被证明通过增强血管内皮生长因子（VEGF）介导的神经保护作用，并伴有缺血半球的血管生成，从而改善缺血性中风动物模型的功能恢复。EE 是否也能促进对侧半球的 VEGF 介导的神经保护和血管生成尚不清楚。在这里，我们在大鼠大脑中动脉闭塞/再灌注（MCAO/r）模型中探讨了 EE 对 VEGF 表达和对侧大脑皮质血管生成的影响。我们使用 Western blot 检测法评估了整个对侧大脑皮质中血小板内皮细胞黏附分子-1（CD31）、VEGF 和内皮型一氧化氮合酶（eNOS）的表达水平，但未发现 EE 中饲养的 MCAO/r 大鼠中 CD31、VEGF 或 eNOS 的表达增加，这表明 EE 并未增强整个对侧皮质中 VEGF 和 eNOS 的整体表达或血管生成。我们通过免疫组织化学进一步分析了 EE 的局部作用，发现与饲养在标准笼（SCs）中的大鼠相比，EE 中饲养的 MCAO/r 大鼠双侧扣带回中的造血祖细胞抗原（CD34）阳性内皮祖细胞显著增加。进一步的实验表明，EE 增加了 MCAO/r 大鼠扣带回周围神经元的 VEGF 表达，并强烈上调了 eNOS 的表达。这些结果表明，EE 增强了 MCAO/r 大鼠扣带回及其周围的血管生成、VEGF 表达和 VEGF-eNOS 通路的激活，这与 MCAO/r 大鼠的功能恢复有关。
