远隔缺血后适应通过调节反应性星形胶质细胞的可塑性改善小鼠缺血后脑组织的恢复

Limb remote ischemic post-conditioning mitigates brain recovery in a mouse model of ischemic stroke by regulating reactive astrocytic plasticity

目的星形胶质细胞的可塑性改变可以在脑缺血急性期引起脑水肿,在缺血恢复期改变胶质瘢痕的形成。本实验研究远隔缺血后适应(RIPC)在脑缺血再灌注损伤中对星形胶质细胞可塑性调节。方法脑缺血被诱导通过C57小鼠大脑中动脉短暂性的阻断1 h,在再灌注即刻给予RIPC。结果 RIPC能降低小鼠脑缺血再灌注3 d、14 d大脑半球的水肿、梗死面积,减少脑萎缩,提高神经功能恢复和生存率。而且RIPC能调节星形胶质细胞亚型的比例,在小鼠脑缺血再灌注3 d和14 d,RIPC能降低缺血侧纤维型星形胶质细胞(GFAP)及增加原浆型星形胶质细胞(GS)的表达,并且能够下调GFAPα的水平和上调GFAPδ/GFAPα的比例来调节GFAP的亚型。结论RIPC治疗能调节反应性星形胶质细胞的可塑性,提高缺血后神经功能的恢复。

Objective Maladaptive alterations of astrocytic plasticity may cause brain edema in the acute stage of stroke and glial scar formation in the recovery stage.The present study was designed to investigate the potential regulation of limb remote ischemic post-conditioning (RIPC) on astrocytic plasticity in experimental cerebral ischemia reperfusion injury.Methods Cerebral ischemia was induced by transient middle cerebral artery occlusion (tMCAO) for 1 h in C57BL/6 mice,who were treated with RIPC immediately after reperfusion.Results The results showed that RIPC decreased hemispheric swelling,infarct volume and brain atrophy,and increased neurological function recovery and survival rates of ischemic mice.Moreover,the proportion of astrocyte subtypes was adjusted by RIPC treatment,demonstrated by decreased expression of the fibrous type (glial fibrillary acidic protein,GFAP) and increased expression of the protoplasmic type (glutamine synthetase,GS) after cerebral ischemia-reperfusion.RIPC treatment adjusted the proportion of GFAP subtypes by downregulating the protein level of GFAPa,as well as upregulating the GFAPδ/GFAPa ratio in the ipsilateral side at 3 d and 14 d after reperfusion.Conclusion The results show that RIPC treatment could regulate reactive astrocytic plasticity to promote neurological function recovery following ischemic stroke.