title: Inhibition of adenosine monophosphate-activated protein kinase reduces glial cell-mediated inflammation and induces the expression of Cx43 in astroglias after cerebral ischemia.
abstract: We investigated the protective effect of adenosine monophosphate-activated protein kinase (AMPK) inhibition on cerebral ischemic injury of mice, and characterized the role of AMPK inhibition on astrocytes, microglias, and neuroinflammation. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in male Kunming mice, and Compound C was used to inhibit AMPK activity. The neurobehavioral scores, infarct volumes, phosphorylation of AMPK, activation of the glial cells, levels of connexin 43 (Cx43), and related inflammatory mediators were affected by the presence or absence of AMPK inhibitor Compound C. AMPK was activated after cerebral ischemia. AMPK inhibition reduced infarct size and improved neurological outcomes after 24h reperfusion of mice. Furthermore, our study revealed that the mechanisms of neuroprotection of AMPK inhibition may be as follows: (1) inhibiting the excessive activation of astrocyte and microglia cells, (2) stabilizing the expression of protective proteins such as Cx43 in astroglias, and (3) inhibiting the release of microglial pro-inflammatory factors. These results demonstrated that AMPK inhibition attenuated cerebral ischemic injury, at least in part, by glial cell-mediated protective effects in mice.
authors.affiliation: Xinjiang Clinical Medical College, Anhui Medical University, Hefei, China; Department of Neurology, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Neurology, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Bu
authors.affiliation: Department of Neurology, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Dang
authors.affiliation: Department of Neurology, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sha
authors.affiliation: Department of Neurology, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Department of Neurology, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, China.
authors.forename: A I
authors.initials: AI
authors.lastname: Shan-jiang
authors.affiliation: Department of Neurology, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Xinjiang Clinical Medical College, Anhui Medical University, Hefei, China; Department of Neurology, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi, China. Electronic address: zhuyixinjiang@sina.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D018031:Connexin 43 / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011897:Random Allocation; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*
chemical_list: D018031:Connexin 43; C543076:GJA1 protein, mouse; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Astrocyte; Cerebral ischemia-reperfusion injury; Cx43; Microglia; Neuroinflammation