Mild hypothermia alleviates early brain injury after subarachnoid hemorrhage via suppressing pyroptosis through AMPK/NLRP3 inflammasome pathway in rats.
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| Abstract |
As a subtype of stroke, subarachnoid hemorrhage (SAH) has a notoriously high rate of disability and mortality owing to the lack of effective intervention. Early brain injury (EBI) is the main factor responsible for the dismal prognosis of SAH patients. The current study intends to explore the molecular mechanism underlying the effect of MH on EBI after SAH from a novel perspective of pyroptosis, a highly specific inflammatory programmed cell death, in the SAH rat model. Sprague-Dawley (SD) rats were divided into different groups in accordance with various treatments. In the treatment group, the rats underwent mild hypothermia for 4 h after modeling; in the inhibitor group, Compound C (an inhibitor of AMPK) was administered intravenous injections (i.v.) 30 min before modeling. Neurological score, neuronal death, brain water content, inflammatory reaction, and expression levels of pyroptosis-related proteins were evaluated in the rats. Our results indicate that the MH therapy significantly increased the neurological score and assuaged brain edema, neuronal injury, and inflammatory reaction induced by SAH. Meanwhile, MH therapy upregulated the level of AMPK phosphorylation whereas downregulated the protein expressions of NLRP3, ASC, cleaved caspase-1, GSDMD, IL-1β, and IL-18. The reversed effect of MH therapy by Compound C concretely indicated that MH therapy inhibited pyroptosis through an AMPK-dependent pathway. Our study also found that MH therapy potently curbed the increasing trend of brain temperature (BT), rectal temperature (RT), and ICP after SAH. Taken together, our data indicate that the neuroprotective effects of MH therapy were manifested by inhibiting pyroptosis via the AMPK/NLRP3 inflammasome pathway, which may serve as a promising therapy for the intervention of SAH.
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| Authors | Zhaopeng Zhou, Zhuanghua Liu, Chenxu Zhang, Wang Zhang, Chunlei Zhang, Tao Chen, Yuhai Wang |
| Journal | Brain research bulletin (Brain Res Bull) Vol. 193 Pg. 72-83 (Feb 2023) ISSN: 1873-2747 [Electronic] United States |
| PMID | 36535306 (Publication Type: Journal Article) |
| Copyright | Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. |
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