Enriched environment promotes post-stroke angiogenesis through astrocytic interleukin-17A.
Enriched environment promotes post-stroke angiogenesis through astrocytic interleukin-17A.
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DOI：
10.3389/fnbeh.2023.1053877
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发表时间：
2023
影响因子：
3
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中科院分区：
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我们以前的研究表明，丰富的环境（EE）的保护作用可能与星形胶质细胞增殖和血管生成。然而，星形胶质细胞与EE条件下血管生成的关系仍需要进一步研究。本研究探讨了EE对脑缺血/再灌注（I/R）损伤后星形胶质细胞白细胞介素-17A（IL-17 A）依赖性血管生成的神经保护作用。通过大脑中动脉闭塞（MCAO）120 min再灌注建立大鼠缺血性中风模型，然后将大鼠饲养在EE或标准条件下。进行了一系列行为测试，包括改良神经系统严重程度评分（mNSS）和旋转棒测试。采用氯化三苯基四氮唑（TTC）染色法测定脑梗死体积。通过免疫荧光和Western blotting检测CD 34蛋白水平，Western blotting和实时定量PCR（RT-qPCR）检测IL-17 A、血管内皮生长因子（VEGF）、血管生成相关因子白细胞介素-6（IL-6）、JAK 2和STAT 3的蛋白和mRNA水平，评价血管生成水平。我们发现，EE促进功能恢复，减少梗死体积，并增强血管生成相比，在标准条件下的大鼠。EE大鼠星形胶质细胞中IL-17 A的表达也增加。EE治疗增加了微血管密度（MVD）水平，促进了半暗带中CD 34、VEGF、IL-6、JAK 2和STAT 3的表达，而侧脑室注射IL-17 A中和抗体则减弱了EE介导的功能恢复和血管生成。本研究揭示了星形胶质细胞IL-17 A在EE介导的血管新生和I/R损伤后功能恢复中的可能神经保护机制，为EE在脑卒中患者的临床应用提供了理论依据，并为IL-17 A介导的脑卒中恢复期神经修复机制的研究开辟了新的思路。
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.
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影响因子：
4.6
作者：
Kühn S;Düzel S;Eibich P;Krekel C;Wüstemann H;Kolbe J;Martensson J;Goebel J;Gallinat J;Wagner GG;Lindenberger U
通讯作者：
Lindenberger U
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影响因子：
7
作者：
Chen JY;Yu Y;Yuan Y;Zhang YJ;Fan XP;Yuan SY;Zhang JC;Yao SL
通讯作者：
Yao SL
地奥司明通过激活小鼠 JAK2/STAT3 信号通路来防止脑缺血/再灌注损伤
影响因子：
3.3
作者：
Liu, X.;Zhang, X.;Wang, X.
通讯作者：
Wang, X.
影响因子：
3.9
作者：
Abdel-Razik, Ahmed;Mousa, Nasser;Eldars, Waleed
通讯作者：
Eldars, Waleed
影响因子：
14.5
作者：
Gertz, Karen;Kronenberg, Golo;Endres, Matthias
通讯作者：
Endres, Matthias