Metformin Inhibits NLR Family Pyrin Domain Containing 3 (NLRP)-Relevant Neuroinflammation via an Adenosine-5'-Monophosphate-Activated Protein Kinase (AMPK)-Dependent Pathway to Alleviate Early Brain Injury After Subarachnoid Hemorrhage in Mice.
Metformin Inhibits NLR Family Pyrin Domain Containing 3 (NLRP)-Relevant Neuroinflammation via an Adenosine-5'-Monophosphate-Activated Protein Kinase (AMPK)-Dependent Pathway to Alleviate Early Brain Injury After Subarachnoid Hemorrhage in Mice.
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DOI：
10.3389/fphar.2022.796616
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发表时间：
2022
影响因子：
5.6
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Jin L;Jin F;Guo S;Liu W;Wei B;Fan H;Li G;Zhang X;Su S;Li R;Fang D;Duan C;Li X
神经炎症在蛛网膜下腔出血(SAH)后早期脑损伤(EBI)的发病机制中起关键作用。以往的研究表明，二甲双胍在多种中枢神经系统疾病中具有抗炎和促进功能恢复的作用。我们设计这项研究是为了研究二甲双胍对蛛网膜下腔出血后EBI的影响。我们的结果表明，二甲双胍的使用减轻了SAH引起的脑水肿、行为障碍、细胞凋亡和神经元损伤。二甲双胍也能抑制SAH诱导的NLRP3相关的炎症反应和小胶质细胞的激活。然而，我们发现化合物C阻断AMPK减弱了二甲双胍对EBI的神经保护作用。综上所述，我们的研究结果表明，二甲双胍通过AMPK依赖的方式抑制神经炎症，通过调节NLRP3相关促炎因子的产生和小胶质细胞的激活来发挥其神经保护作用。
Neuroinflammation plays a key role in the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Previous studies have shown that metformin exerts anti-inflammatory effects and promotes functional recovery in various central nervous system diseases. We designed this study to investigate the effects of metformin on EBI after SAH. Our results indicate that the use of metformin alleviates the brain edema, behavioral disorders, cell apoptosis, and neuronal injury caused by SAH. The SAH-induced NLRP3-associated inflammatory response and the activation of microglia are also suppressed by metformin. However, we found that the blockade of AMPK with compound C weakened the neuroprotective effects of metformin on EBI. Collectively, our findings indicate that metformin exerts its neuroprotective effects by inhibiting neuroinflammation in an AMPK-dependent manner, by modulating the production of NLRP3-associated proinflammatory factors and the activation of microglia.
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影响因子：
11.4
作者：
Fan H;Ding R;Liu W;Zhang X;Li R;Wei B;Su S;Jin F;Wei C;He X;Li X;Duan C
通讯作者：
Duan C
DOI：
10.1016/j.bbi.2020.09.016
发表时间：
2021-01
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Hu X;Yan J;Huang L;Araujo C;Peng J;Gao L;Liu S;Tang J;Zuo G;Zhang JH
通讯作者：
Zhang JH
影响因子：
6.9
作者：
Fujii, Mutsumi;Yan, Junhao;Rolland, William B.;Soejima, Yoshiteru;Caner, Basak;Zhang, John H.
通讯作者：
Zhang, John H.
影响因子：
8.3
作者：
GARCIA, JH;WAGNER, S;HU, XJ
通讯作者：
HU, XJ
影响因子：
11.4
作者：
Jia, Yifan;Cui, Ruixia;Zhang, Jingyao
通讯作者：
Zhang, Jingyao