Sevoflurane postconditioning attenuates reactive astrogliosis and glial scar formation after ischemia-reperfusion brain injury
Sevoflurane postconditioning attenuates reactive astrogliosis and glial scar formation after ischemia-reperfusion brain injury
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七氟烷后处理可减轻缺血再灌注脑损伤后反应性星形胶质细胞增生和神经胶质疤痕形成
DOI：
10.1016/j.neuroscience.2017.05.004
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发表时间：
2017
期刊：
影响因子：
3.3
通讯作者：
Hui-Ling Zhang
中科院分区：
文献类型：
--
作者：
Yong-Ming Zhu;Xue Gao;Yong Ni;Wei Li;Thomas A. Kent;Shi-Gang Qiao;Chen Wang;Xiao-Xuan Xu;Hui-Ling Zhang
脑缺血导致星形胶质细胞活化和神经胶质疤痕形成。神经胶质疤痕可以抑制恢复期的轴突再生。已证明七氟醚对缺血性中风具有神经保护作用，但其对缺血诱导的星形胶质细胞增生和神经胶质疤痕形成的影响尚不清楚。本研究旨在研究七氟醚后处理对体内和体外缺血性中风模型中星形胶质细胞增生和神经胶质疤痕形成的影响。结果显示，2.5%七氟醚后处理可显着减少梗塞体积，改善神经功能缺损。它还可以降低梗死周围区域胶质疤痕标志物胶质纤维酸性蛋白（GFAP）、神经聚糖和磷酸聚糖的表达，并显着减少缺血/再灌注（I/R）后胶质疤痕的厚度。与体内数据一致，在缺氧和缺糖/复氧（OGD/Re）模型中，七氟烷后处理可以保护星形胶质细胞免受OGD/Re诱导的损伤，降低GFAP、神经聚糖和磷酸聚糖的表达。进一步的研究表明，七氟醚后处理可以下调 Lamp1 和活性组织蛋白酶 B 的表达，并阻断 I/R 或 OGD/Re 诱导的组织蛋白酶 B 从溶酶体释放到细胞质中。为了证实抑制组织蛋白酶B是否可以减轻胶质疤痕的形成，我们使用组织蛋白酶B抑制剂CA-074Me作为阳性对照。结果表明，抑制组织蛋白酶B可以降低GFAP、neurocan和phosphacan的表达。总之，七氟醚后处理可以减轻缺血性中风后星形胶质细胞增生和神经胶质疤痕的形成，与抑制溶酶体组织蛋白酶 B 的激活和释放有关。
Cerebral ischemia leads to astrocyte’s activation and glial scar formation. Glial scar can inhibit axonal regeneration during the recovery phase. It has demonstrated that sevoflurane has neuroprotective effects against ischemic stroke, but its effects on ischemia-induced formation of astrogliosis and glial scar are unknown. This study was designed to investigate the effect of sevoflurane postconditioning on astrogliosis and glial scar formation in ischemic stroke model bothin vivoandin vitro. The results showed that 2.5% of sevoflurane postconditioning could significantly reduce infarction volume and improve neurologic deficits. And it could also decrease the expression of the glial scar marker glial fibrillary acidic protein (GFAP), neurocan and phosphacan in the peri-infarct region and markedly reduce the thickness of glial scar after ischemia/reperfusion (I/R). Consistent with thein vivodata, in the oxygen and glucose deprivation/reoxygenation (OGD/Re) model, sevoflurane postconditioning could protect astrocyte against OGD/Re-induced injury, decrease the expression of GFAP, neurocan and phosphacan. Further studies demonstrated that sevoflurane postconditioning could down-regulate the expression of Lamp1 and active cathepsin B, and block I/R or OGD/Re-induced release of cathepsin B from the lysosomes into cytoplasm. In order to confirm whether inhibition of cathepsin B could attenuate the formation of glial scar, we used cathepsin B inhibitor CA-074Me as a positive control. The results showed that inhibition of cathepsin B could decrease the expression of GFAP, neurocan and phosphacan. Taken together, sevoflurane postconditioning can attenuate astrogliosis and glial scar formation after ischemic stroke, associating with inhibition of the activation and release of lysosomal cathepsin B.