Dexmedetomidine Inhibits Gasdermin D-Induced Pyroptosis via the PI3K/AKT/GSK3β Pathway to Attenuate Neuroinflammation in Early Brain Injury After Subarachnoid Hemorrhage in Rats.
Dexmedetomidine Inhibits Gasdermin D-Induced Pyroptosis via the PI3K/AKT/GSK3β Pathway to Attenuate Neuroinflammation in Early Brain Injury After Subarachnoid Hemorrhage in Rats.
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DOI：
10.3389/fncel.2022.899484
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发表时间：
2022
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
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作者：
蛛网膜下腔出血(SAH)是一种危及生命的卒中，可导致严重的脑损伤。下垂在蛛网膜下腔出血后早期脑损伤(EBI)中起关键作用。以往的报道表明，右旋美托咪定(Dex)可抑制SAH所致的脑水肿、细胞凋亡和神经元损伤。本研究采用SAH大鼠模型，观察地塞米松对SAH后EBI下垂的影响，并探讨其作用机制。SAH后EBI内可见小胶质细胞下垂。地塞米松通过减少嗜热性下垂执行剂GSDMD而明显减轻小胶质细胞的嗜酸性下垂，并抑制SAH诱导的促炎细胞因子的释放。此外，PI3K抑制剂LY294002取消了地塞米松降低GSDMD的作用。综上所述，我们的研究结果表明，地塞米松通过激活PI3K/AKT/GSK3β通路减少蛛网膜下腔出血后脑出血后小胶质细胞松弛。
Subarachnoid hemorrhage (SAH) is one kind of life-threatening stroke, which leads to severe brain damage. Pyroptosis plays a critical role in early brain injury (EBI) after SAH. Previous reports suggest that SAH-induced brain edema, cell apoptosis, and neuronal injury could be suppressed by dexmedetomidine (Dex). In this study, we used a rat model of SAH to investigate the effect of Dex on pyroptosis in EBI after SAH and to determine the mechanisms involved. Pyroptosis was found in microglia in EBI after SAH. Dex significantly alleviated microglia pyroptosis via reducing pyroptosis executioner GSDMD and inhibited the release of proinflammatory cytokines induced by SAH. Furthermore, the reduction of GSDMD by Dex was abolished by the PI3K inhibitor LY294002. In conclusion, our data demonstrated that Dex reduces microglia pyroptosis in EBI after SAH via the activation of the PI3K/AKT/GSK3β pathway.
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DOI：
10.1186/cc5958
发表时间：
2007
期刊：
Critical care (London, England)
影响因子：
--
作者：
Keyrouz SG;Diringer MN
通讯作者：
Diringer MN
影响因子：
9.3
作者：
Chen M;Li X;Zhang X;He X;Lai L;Liu Y;Zhu G;Li W;Li H;Fang Q;Wang Z;Duan C
通讯作者：
Duan C
影响因子：
4.3
作者：
Cheng X;Hu J;Wang Y;Ye H;Li X;Gao Q;Li Z
通讯作者：
Li Z
蛛网膜下腔出血后过氧化还原蛋白 2 通过与 Toll 样受体 4 相互作用激活小胶质细胞
影响因子：
9.3
作者：
Lu Y;Zhang XS;Zhang ZH;Zhou XM;Gao YY;Liu GJ;Wang H;Wu LY;Li W;Hang CH
通讯作者：
Hang CH
影响因子：
--
作者：
Jacobs KM;Bhave SR;Ferraro DJ;Jaboin JJ;Hallahan DE;Thotala D
通讯作者：
Thotala D