title: Propofol protects against focal cerebral ischemia via inhibition of microglia-mediated proinflammatory cytokines in a rat model of experimental stroke.
abstract: Ischemic stroke induces microglial activation and release of proinflammatory cytokines, contributing to the expansion of brain injury and poor clinical outcome. Propofol has been shown to ameliorate neuronal injury in a number of experimental studies, but the precise mechanisms involved in its neuroprotective effects remain unclear. We tested the hypothesis that propofol confers neuroprotection against focal ischemia by inhibiting microglia-mediated inflammatory response in a rat model of ischemic stroke. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by 24 h of reperfusion. Propofol (50 mg/kg/h) or vehicle was infused intravenously at the onset of reperfusion for 30 minutes. In vehicle-treated rats, MCAO resulted in significant cerebral infarction, higher neurological deficit scores and decreased time on the rotarod compared with sham-operated rats. Propofol treatment reduced infarct volume and improved the neurological functions. In addition, molecular studies demonstrated that mRNA expression of microglial marker Cd68 and Emr1 was significantly increased, and mRNA and protein expressions of proinflammatory cytokines tumor necrosis factor-α, interleukin-1β and interleukin-6 were augmented in the peri-infarct cortical regions of vehicle-treated rats 24 h after MCAO. Immunohistochemical study revealed that number of total microglia and proportion of activated microglia in the peri-infarct cortical regions were markedly elevated. All of these findings were ameliorated in propofol-treated rats. Furthermore, vehicle-treated rats had higher plasma levels of interleukin-6 and C-reactive protein 24 h after MCAO, which were decreased after treatment with propofol. These results suggest that propofol protects against focal cerebral ischemia via inhibition of microglia-mediated proinflammatory cytokines. Propofol may be a promising therapeutic agent for the treatment of ischemic stroke and other neurodegenerative diseases associated with microglial activation.
authors.affiliation: Department of Operating Room, Children's Hospital, Chongqing Medical University, Chongqing, China ; Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Hematopoietic Stem Cell Transplantation and Gene Therapy Center, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China ; State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Third Military Medical University, Chongqing, China ; Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zailiang
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Operating Room, Children's Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Xurong
authors.initials: X
authors.lastname: Tang
authors.affiliation: Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital, Chongqing Medical University, Chongqing, China ; Department of Anesthesiology, Children's Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D015415:Biomarkers; D002545:Brain Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D020244:Infarction, Middle Cerebral Artery; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D015742:Propofol