Trek 1 Ameliorates Secondary Brain Injury By Regulating Inflammatory Microenvironment Via Cx3 Cl1cx3 Cr1 Pathway After Intracerebral Hemorrhage Yongkang Fang Dilinuer Sadike Na Jiang Yuan Xu Yao Wang Yang Liu Xiaolong Zheng Zhou Zhu Suiqiang Zhu Wei Wang Feng Xu Minjie Xie by Yongkang Fang & Dilinuer Sadike & Na Jiang & Yuan Xu & Yao Wang & Yang Liu & Xiaolong Zheng & Zhou Zhu & Suiqiang Zhu & Wei Wang & Feng Xu & Minjie Xie 101007/S12035025049501 instant download after payment.

Neuroinfammation plays a pivotal role in the pathogenesis of secondary brain injury (SBI) after intracerebral hemorrhage (ICH). TREK-1 is a background potassium channel, and its role in regulating neuroinfammation after ICH remains unclear. In this study, ICH models were induced in wide-type (WT) and TREK knockout mice via intra-striatal administration of collagenase. Additionally, WT ICH mice were treated with the TREK-1 agonist ML67-33. Immunofuorescence, western blot, quantitative real-time PCR, enzyme-linked immunosorbent assay, and RNA-sequencing were performed to determine the role and the mechanism of TREK-1 in regulating neuroinfammation after ICH. The results indicate that TREK-1 defciency exacerbated microglia/macrophages activation and pro-infammatory polarization, as well as the infux of infammatory cytokines and peripheral infammatory cells compared to WT ICH mice. Conversely, activation of TREK-1 attenuated the infammatory response and SBI post-ICH. These efects may be mediated through the CX3CL1-CX3CR1 pathway, as validated by specifc inhibitors AZD8797. This study identifed TREK-1 as a crucial modulator in alleviating SBI by regulating the infammatory microenvironment via the CX3CL1-CX3CR1 pathway.Keywords Intracerebral hemorrhage · TREK- 1 · Secondary brain injury · Infammatory microenvironment · CX3 CL1-CX3 CR1