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.

中文翻译：

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丰富的环境增强了缺血性中风大鼠扣带周围的血管生成

丰富的环境 (EE) 已被证明可以通过增强血管内皮生长因子 (VEGF) 介导的神经保护以及缺血半球的血管生成来改善缺血性中风动物模型的功能恢复。EEs 是否也促进对侧半球 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) 模型中探索了 EEs 对 VEGF 表达和对侧大脑皮层内血管生成的影响。我们使用蛋白质印迹法评估了整个对侧大脑皮层中血小板内皮细胞粘附分子-1 (CD31)、VEGF 和内皮一氧化氮合酶 (eNOS) 的表达水平，但未发现 CD31、VEGF 的表达增加, 或 eNOS 在饲养在 EE 中的 MCAO/r 大鼠中，这表明 EE 没有增强 VEGF 和 eNOS 的整体表达或整个对侧皮层中的血管生成。我们通过免疫组织化学进一步分析了 EEs 的局部作用，发现在 EEs 中的 MCAO/r 大鼠双侧扣带内和周围，造血祖细胞抗原 - (CD34-) 阳性内皮祖细胞与被安置的大鼠相比显着增加。在标准笼子 (SC) 中。进一步的实验表明，EEs 增加了 MCAO/r 大鼠扣带周围神经元 VEGF 的表达，并强烈上调了 eNOS 的表达。这些结果表明，EEs 增强了血管生成、VEGF 表达和 VEGF-eNOS 通路在 MCAO/r 大鼠扣带内和/或周围的激活，