CCL5/CCR5-mediated peripheral inflammation exacerbates blood-brain barrier disruption after intracerebral hemorrhage in mice

作者全名："Lin, Jie; Xu, Ya; Guo, Peiwen; Chen, Yu-Jie; Zhou, Jiru; Xia, Min; Tan, Binbin; Liu, Xin; Feng, Hua; Chen, Yujie"

作者地址："[Lin, Jie; Xu, Ya; Guo, Peiwen; Chen, Yu-Jie; Zhou, Jiru; Xia, Min; Tan, Binbin; Feng, Hua; Chen, Yujie] Army Med Univ, Mil Med Univ 3, Southwest Hosp, Dept Neurosurg, 29 Gaotanyan St, Chongqing 400038, Peoples R China; [Lin, Jie; Xu, Ya; Guo, Peiwen; Chen, Yu-Jie; Zhou, Jiru; Xia, Min; Tan, Binbin; Feng, Hua; Chen, Yujie] Army Med Univ, Mil Med Univ 3, Southwest Hosp, State Key Lab Trauma Burn & Combined Injury, 29 Gaotanyan St, Chongqing 400038, Peoples R China; [Lin, Jie; Xu, Ya; Guo, Peiwen; Chen, Yu-Jie; Zhou, Jiru; Xia, Min; Tan, Binbin; Feng, Hua; Chen, Yujie] Army Med Univ, Mil Med Univ 3, Southwest Hosp, Chongqing Clin Res Ctr Neurosurg, Chongqing 400038, Peoples R China; [Lin, Jie; Xu, Ya; Guo, Peiwen; Chen, Yu-Jie; Zhou, Jiru; Xia, Min; Tan, Binbin; Feng, Hua; Chen, Yujie] Army Med Univ, Mil Med Univ 3, Southwest Hosp, Chongqing Key Lab Precis Neuromed & Neuroregenarat, Chongqing 400038, Peoples R China; [Zhou, Jiru] Chongqing Med Univ, Dept Neurosurg, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Liu, Xin] Army Med Univ, Mil Med Univ 3, Southwest Hosp, Clin Med Res Ctr, Chongqing 400038, Peoples R China"

通信作者："Feng, H; Chen, YJ (通讯作者)，Army Med Univ, Mil Med Univ 3, Southwest Hosp, Dept Neurosurg, 29 Gaotanyan St, Chongqing 400038, Peoples R China.; Feng, H; Chen, YJ (通讯作者)，Army Med Univ, Mil Med Univ 3, Southwest Hosp, State Key Lab Trauma Burn & Combined Injury, 29 Gaotanyan St, Chongqing 400038, Peoples R China.; Feng, H; Chen, YJ (通讯作者)，Army Med Univ, Mil Med Univ 3, Southwest Hosp, Chongqing Clin Res Ctr Neurosurg, Chongqing 400038, Peoples R China.; Feng, H; Chen, YJ (通讯作者)，Army Med Univ, Mil Med Univ 3, Southwest Hosp, Chongqing Key Lab Precis Neuromed & Neuroregenarat, Chongqing 400038, Peoples R China."

来源：JOURNAL OF TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000952174800004

JCR分区：Q1

影响因子：6.1

年份：2023

卷号：21

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Intracerebral hemorrhage; Blood-brain barrier; C-C chemokine receptor 5; Peripheral inflammation; Neuroinflammation; Brain-periphery crosstalk

摘要："BackgroundOwing to metabolic disequilibrium and immune suppression, intracerebral hemorrhage (ICH) patients are prone to infections; according to a recent global analysis of stroke cases, approximately 10 million new-onset ICH patients had experienced concurrent infection. However, the intrinsic mechanisms underlying the effects of infection related peripheral inflammation after ICH remain unclear.MethodsLipopolysaccharide (LPS) was intraperitoneally injected into ICH model mice to induce peripheral inflammation. Neurobehavioral deficits, blood-brain barrier (BBB) disruption, and the expression of CCR5, JAK2, STAT3, and MMP9 were evaluated after treatment with recombinant CCL5 (rCCL5) (a CCR5 ligand), maraviroc (MVC) (an FDA-approved selective CCR5 antagonist), or JAK2 CRISPR plasmids.ResultsOur study revealed that severe peripheral inflammation increased CCL5/CCR5 axis activation in multiple inflammatory cell types, including microglia, astrocytes, and monocytes, and aggravated BBB disruption and neurobehavioral dysfunction after ICH, possibly in part through the JAK2/STAT3 signaling pathway.ConclusionsCCR5 might be a potential target for the clinical treatment of infection-induced exacerbation of BBB disruption following ICH."

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