Enriched housing promotes post-stroke functional recovery through astrocytic HMGB1-IL-6-mediated angiogenesis.

Enriched housing promotes post-stroke functional recovery through astrocytic HMGB1-IL-6-mediated angiogenesis.
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丰富的住房通过星形细胞 HMGB1-IL-6 介导的血管生成促进中风后功能恢复。

DOI:
10.1038/cddiscovery.2017.54
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发表时间:
2017
影响因子:
7
通讯作者:
Yao SL
Yao SL
中科院分区:
医学2区
文献类型:
--
作者:
Chen JY;Yu Y;Yuan Y;Zhang YJ;Fan XP;Yuan SY;Zhang JC;Yao SL

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丰富的环境(EE)被证明可以促进缺血性卒中后的血管生成、神经发生和功能恢复。然而,其潜在机制仍不清楚。C57 BL/6小鼠大脑中动脉闭塞(60分钟),然后再灌注,然后将小鼠圈养在标准环境(SE)或EE。在这里,我们发现,缺血后EE表现出减少抑郁和焦虑样行为,并促进血管生成和功能恢复相比,SE小鼠。高迁移率族蛋白1(HMGB 1)抑制剂治疗的EE小鼠中风后抑郁和焦虑样行为增加,血管生成和功能恢复减少。EE小鼠星形胶质细胞HMGB 1和IL-6表达增加。用重组HMGB 1(rHMGB 1)处理的EE小鼠降低了IL-6和p-AKT的水平,而用重组HMGB 1(rHMGB 1)处理的EE小鼠增加了IL-6和p-AKT的水平。在EE小鼠中用抗IL-6中和抗体阻断IL-6可减弱EE介导的血管生成和功能恢复。此外,我们的体外数据显示,在原代星形胶质细胞培养中,rHMGB 1促进活化星形胶质细胞中IL-6的表达。PI 3 K/AKT信号通路参与HMGB 1介导的星形胶质细胞IL-6表达。因此,我们的研究结果揭示了一个以前未知的属性HMGB 1/IL-6信号通路在EE介导的血管生成和功能恢复缺血性中风后。
Enriched environment (EE) is shown to promote angiogenesis, neurogenesis and functional recovery after ischemic stroke. However, the underlying mechanisms remain unclear. C57BL/6 mice underwent middle cerebral artery occlusion (60 min) followed by reperfusion, after which mice were housed in either standard environment (SE) or EE. Here we found that post-ischemic EE exhibited decreased depression and anxiety-like behavior, and promoted angiogenesis and functional recovery compared to SE mice. EE mice treated with high-mobility group box-1 (HMGB1) inhibitor glycyrrhizin had an increased post-stroke depression and anxiety-like behavior, and the angiogenesis and functional recovery were decreased. HMGB1 and interleukin-6 (IL-6) expression in astrocyte were increased in EE mice. EE mice treated with glycyrrhizin decreased, whereas EE mice treated with recombinant HMGB1 (rHMGB1) increased the levels of IL-6 and p-AKT. Blockade of IL-6 with anti-IL-6-neutralizing antibody in EE mice attenuated EE-mediated angiogenesis and functional recovery. Furthermore, our in vitro data revealed that in primary astrocyte cultures rHMGB1 promoted the expression of IL-6 in activated astrocytes. PI3K/AKT signaling pathway was involved in HMGB1-mediated expression of astrocytic IL-6. Thus, our results reveal a previously uncharacterized property of HMGB1/IL-6 signaling pathway in EE-mediated angiogenesis and functional recovery after ischemic stroke.
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