title: Neuroprotection by platelet-activating factor acetylhydrolase in a mouse model of transient cerebral ischemia.
abstract: Neuronal damage after transient cerebral ischemia is exacerbated by signaling pathways involving activated platelet-activating factor (PAF) and ameliorated by PAF-acetylhydrolase (PAF-AH); but whether cerebral neurons can be rescued by human recombinant PAF-AH (rPAF-AH) remains unknown. Adult male mice underwent a 60 min middle cerebral artery occlusion (MCAO) and reperfusion for 24h. Then, the mice received intravenous tail injections with different drugs. Neurological behavioral function was evaluated by Bederson's test, and cerebral infarction volume was assessed with tetrazolium chloride (TTC) staining. mRNA and protein expression levels of matrix metalloproteinase-2 (MMP-2, collagenase-1), MMP-9 (gelatinase-B), and vascular endothelial growth factor (VEGF) were determined by quantitative real-time PCR (RT-PCR) and western blot analysis, respectively. Compared with the vehicle group, rPAF-AH significantly improved sensorimotor function (42%, P=0.0001). The volume of non-infarcted brain tissue was increased by the rPAF-AH treatment (16.3±4.6% vs. 46.0±10.3%, respectively). rPAF-AH significantly reduced mRNA and protein levels of MMP-2 and MMP-9, but increased the mRNA (P<0.001) and protein levels (P<0.01) of VEGF. These results demonstrate that rPAF-AH provides neuroprotection against ischemic injury. Neuroprotection might be induced not only by decrease in MMP-2 and MMP-9 expression, but also by increased VEGF expression.
authors.affiliation: Department of Neurology, First Affiliated Hospital of Guangzhou Medical University, 510120 Guangzhou, Guangdong, China; Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, 510080 Guangzhou, China.
authors.forename: Yijuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, 510080 Guangzhou, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, 510080 Guangzhou, China.
authors.forename: Chengbo
authors.initials: C
authors.lastname: Dai
authors.affiliation: Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, 510080 Guangzhou, China.
authors.forename: Guixian
authors.initials: G
authors.lastname: Ma
authors.affiliation: Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, 510080 Guangzhou, China.
authors.forename: Yuhu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, 510080 Guangzhou, China. Electronic address: xiongzhang2012@126.com.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, First Affiliated Hospital of Guangzhou Medical University, 510120 Guangzhou, Guangdong, China.
authors.forename: Zhuohua
authors.initials: Z
authors.lastname: Wu
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: MCAO; Matrix metalloproteinase; PAF-acetylhydrolase; Transient ischemia; Treatment; VEGF