title: Neuroprotective effects of bisperoxovanadium on cerebral ischemia by inflammation inhibition.
abstract: PTEN is a dual specificity phosphatase and is implicated in inflammation and apoptosis of cerebral ischemia and reperfusion (I/R) injury. Bisperoxovanadium (Bpv), a specific inhibitor of PTEN's phosphatase activity, has demonstrated powerful neuroprotective properties. We investigated the neuroprotective roles of Bpv in the rat model of middle cerebral artery occlusion (MCAO) cerebral I/R injury, and explored the modulation of inflammatory mediators and PI3K/Akt/GSK-3β pathways by Bpv. Our results showed that treatment with Bpv (0.2 mg/kg/day) significantly decreased neurological deficit scores at 7 days after MCAO and infarct volume at 4 days after MCAO. The IL-10 concentration was increased and TNF-α concentration was decreased in the ischemic boundary zone of the cerebral cortex at 4 days after MCAO by Bpv. Furthermore, Bpv (0.2 mg/kg/day) treatment significantly reduced PTEN mRNA and protein levels and increased PI3K, Akt and p-GSK-3β proteins expression in the ischemic boundary zone of the cerebral cortex at 4 days after MCAO. In conclusions, Bpv treatment demonstrates neuroprotective effects on cerebral ischemia and reperfusion injury of ischemic stroke rats and is associated with its modulation of inflammatory mediator production and up-regulation of PTEN downstream proteins PI3K, Akt and p-GSK-3β.
authors.affiliation: Department of Neurology, Wujin Hospital Affiliated to Jiangsu University, Changzhou 213002, Jiangsu, PR China.
authors.forename: Lun-Lin
authors.initials: LL
authors.lastname: Mao
authors.affiliation: Department of Neurology, Wujin Hospital Affiliated to Jiangsu University, Changzhou 213002, Jiangsu, PR China. Electronic address: haodljs@163.com.
authors.forename: Dong-Lin
authors.initials: DL
authors.lastname: Hao
authors.affiliation: Department of Neurology, Changhai Hospital Affiliated to the Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Mao
authors.affiliation: Department of Neurology, Wujin Hospital Affiliated to Jiangsu University, Changzhou 213002, Jiangsu, PR China.
authors.forename: Yuan-Feng
authors.initials: YF
authors.lastname: Xu
authors.affiliation: Department of Neurology, Wujin Hospital Affiliated to Jiangsu University, Changzhou 213002, Jiangsu, PR China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Huang
authors.affiliation: Department of Neurology, Wujin Hospital Affiliated to Jiangsu University, Changzhou 213002, Jiangsu, PR China.
authors.forename: Bo-Na
authors.initials: BN
authors.lastname: Wu
authors.affiliation: Department of Neurology, Wujin Hospital Affiliated to Jiangsu University, Changzhou 213002, Jiangsu, PR China.
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Wang
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D017968:Vanadium Compounds / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D017968:Vanadium Compounds; C472777:bisperoxovanadium; D016753:Interleukin-10; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat
keywords: (GSK-3β); Akt; Bisperoxovanadium (Bpv); Glycogen synthase kinase 3β; Ischemic stroke; Middle cerebral artery occlusion (MCAO); Phosphatidylinositol 3-kinase (PI3K)