title: MCP-1-mediated activation of microglia promotes white matter lesions and cognitive deficits by chronic cerebral hypoperfusion in mice.
abstract: Microglia activation played a vital role in the pathogenesis of white matter lesions (WMLs) by chronic cerebral hypoperfusion. In addition, hypoxia induced up-regulated expression of MCP-1, promotes the activation of microglia. However, the role of MCP-1-mediated microglia activation in chronic cerebral ischemia is still unknown. To explore that, chronic cerebral hypoperfusion model was established by permanent stenosis of bilateral common carotid artery in mice. The activation of microglia and the related signal pathway p38MAPK/PKC in white matter, and working memory of mice were observed. We found that stenosis of common carotid arteries could induce MCP-1-mediated activation of microglia through p38MAPK/PKC pathway and white matter lesions. Taken together, our findings represent a novel mechanism of MCP-1 involved in activation of microglia and provide a novel therapeutical strategy for chronic cerebral hypoperfusion.
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China; Department of Neurosurgery, The 476th Hospital of PLA, Fuzhou, Fujian 350025, China.
authors.forename: Bangqing
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
authors.forename: Kuang
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
authors.forename: Zulu
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
authors.forename: Xuenong
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
authors.forename: Changlong
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
authors.forename: Qijiang
authors.initials: Q
authors.lastname: Xiong
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China. Electronic address: yangzhao5140@sohu.com.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D016893:Carotid Stenosis / Q000378:metabolism* / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003071:Cognition; D020935:MAP Kinase Signaling System; D008297:Male; D008570:Memory, Short-Term; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D066127:White Matter / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Chronic cerebral hypoperfusion; MCP-1; Microglia; White matter lesions