Subanesthetic isoflurane abates ROS-activated MAPK/NF-κB signaling to repress ischemia-induced microglia inflammation and brain injury.
Subanesthetic isoflurane abates ROS-activated MAPK/NF-κB signaling to repress ischemia-induced microglia inflammation and brain injury.
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DOI：
10.18632/aging.202349
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发表时间：
2020-12-28
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影响因子：
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通讯作者：
Li J
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文献类型：
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作者：
Yao Z;Liu N;Zhu X;Wang L;Zhao Y;Liu Q;Gao C;Li J
异氟醚对缺血性脑损伤具有保护作用。我们研究了亚麻醉（0.7%）ISO后适应是否能减轻体外氧糖剥夺（OGD）损伤的共培养物（小胶质细胞和神经元）和大脑中动脉闭塞（MCAO）大鼠的炎症和凋亡。我们证明了ISO增强了ogd处理的小胶质细胞和神经元的活力。ISO降低了ogd激发的小胶质细胞中COX2和iNOS的表达和激活。ISO抑制ogd暴露的小胶质细胞中肿瘤坏死因子-α、白细胞介素(IL)-1β、IL-6、IL-8和单核细胞趋化蛋白-1的产生。在ogd刺激的小胶质细胞和神经元中，ISO也减少了核小体断裂和caspase-3活性，但增加了线粒体膜电位。在机制上，ISO通过阻断ROS调控的p38 MAPK/NF-κ b信号通路抑制ogd诱导的小胶质细胞炎症，并以ROS或no依赖的方式抑制ogd引发的小胶质细胞凋亡。MCAO大鼠体内实验结果与体外实验结果部分一致。这些结果表明，亚麻醉ISO后适应可减轻ogd刺激大鼠小胶质细胞的炎症和凋亡，以及ogd暴露神经元的凋亡和MCAO大鼠脑损伤，提示其可能是一种有效的缺血性脑损伤治疗方法。
Isoflurane (ISO) elicits protective effects on ischemia-induced brain injury. We investigated whether sub-anesthetic (0.7%) ISO post-conditioning attenuates the inflammation and apoptosis in oxygen-glucose deprivation (OGD)-insulted co-cultures (microglia and neurons) in vitro and the brain injury of the middle cerebral arterial occlusion (MCAO) rat. We demonstrated that ISO augmented the viability of OGD-treated microglia and neurons. ISO reduced the expression and activation of COX2 and iNOS in OGD-challenged microglia. ISO repressed the production of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, and monocyte chemoattractant protein-1 in OGD-exposed microglia. ISO also decreased nucleosomal fragmentation and caspase-3 activity but increased mitochondrial membrane potential in OGD-stimulated microglia and neurons. Mechanistically, ISO suppressed OGD-induced microglial inflammation by blocking ROS-regulated p38 MAPK/NF-κB signaling pathway and hampered OGD-triggered microglial apoptosis in a ROS- or NO-dependent fashion. In vivo results with MCAO rats were partly consistent with the in vitro observation. These findings indicate that sub-anesthetic ISO post-conditioning abates the inflammation and apoptosis in OGD-stimulated rat microglia and the apoptosis of OGD-exposed neurons and the brain injuries of MCAO rats, suggesting it as a potentially effective therapeutic approach for ischemic brain damages.