Chen Xiuping, Liu Lingling, Zhong Yingjun, Liu Yang
Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Front Behav Neurosci. 2023 Feb 16;17:1053877. doi: 10.3389/fnbeh.2023.1053877. eCollection 2023.
Our previous studies have revealed that the protective effect of an enriched environment (EE) may be linked with astrocyte proliferation and angiogenesis. However, the relationship between astrocytes and angiogenesis under EE conditions still requires further study. The current research examined the neuroprotective effects of EE on angiogenesis in an astrocytic interleukin-17A (IL-17A)-dependent manner following cerebral ischemia/reperfusion (I/R) injury.
A rat model of ischemic stroke based on middle cerebral artery occlusion (MCAO) for 120 min followed by reperfusion was established, after which rats were housed in either EE or standard conditions. A set of behavior tests were conducted, including the modified neurological severity scores (mNSS) and the rotarod test. The infarct volume was evaluated by means of 2,3,5-Triphenyl tetrazolium chloride (TTC) staining. To evaluate the levels of angiogenesis, the protein levels of CD34 were examined by means of immunofluorescence and western blotting, while the protein and mRNA levels of IL-17A, vascular endothelial growth factor (VEGF), and the angiogenesis-associated factors interleukin-6 (IL-6), JAK2, and STAT3 were detected by western blotting and real-time quantitative PCR (RT-qPCR).
We found that EE promoted functional recovery, reduced infarct volume, and enhanced angiogenesis compared to rats in standard conditions. IL-17A expression in astrocytes was also increased in EE rats. EE treatment increased the levels of microvascular density (MVD) and promoted the expression of CD34, VEGF, IL-6, JAK2, and STAT3 in the penumbra, while the intracerebroventricular injection of the IL-17A-neutralizing antibody in EE rats attenuated EE-mediated functional recovery and angiogenesis.
Our findings revealed a possible neuroprotective mechanism of astrocytic IL-17A in EE-mediated angiogenesis and functional recovery after I/R injury, which might provide the theoretical basis for EE in clinical practise for stroke patients and open up new ideas for the research on the neural repair mechanism mediated by IL-17A in the recovery phase of stroke.
我们之前的研究表明，丰富环境（EE）的保护作用可能与星形胶质细胞增殖和血管生成有关。然而，EE条件下星形胶质细胞与血管生成之间的关系仍需进一步研究。当前研究以星形胶质细胞白细胞介素-17A（IL-17A）依赖的方式，研究了EE对脑缺血/再灌注（I/R）损伤后血管生成的神经保护作用。
建立基于大脑中动脉闭塞（MCAO）120分钟后再灌注的缺血性中风大鼠模型，之后将大鼠饲养在EE或标准条件下。进行了一系列行为测试，包括改良神经功能缺损评分（mNSS）和转棒试验。通过2,3,5-氯化三苯基四氮唑（TTC）染色评估梗死体积。为评估血管生成水平，通过免疫荧光和蛋白质印迹检测CD34的蛋白质水平，同时通过蛋白质印迹和实时定量PCR（RT-qPCR）检测IL-17A、血管内皮生长因子（VEGF）以及血管生成相关因子白细胞介素-6（IL-6）、JAK2和STAT3的蛋白质和mRNA水平。
我们发现，与标准条件下的大鼠相比，EE促进了功能恢复，减小了梗死体积，并增强了血管生成。EE大鼠星形胶质细胞中IL-17A表达也增加。EE处理增加了半暗带微血管密度（MVD）水平，并促进了CD34、VEGF、IL-6、JAK2和STAT3的表达，而在EE大鼠脑室内注射IL-17A中和抗体减弱了EE介导的功能恢复和血管生成。
我们的研究结果揭示了星形胶质细胞IL-17A在EE介导的I/R损伤后血管生成和功能恢复中的一种可能的神经保护机制，这可能为EE在中风患者临床实践中的应用提供理论依据，并为中风恢复阶段IL-17A介导的神经修复机制研究开辟新思路。
