Neuroprotective effects of bisperoxovanadium on cerebral ischemia by inflammation inhibition.
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.
['Mao|Lun-Lin|LL|', 'Hao|Dong-Lin|DL|', 'Mao|Xiao-Wei|XW|', 'Xu|Yuan-Feng|YF|', 'Huang|Ting-Ting|TT|', 'Wu|Bo-Na|BN|', 'Wang|Li-Hui|LH|']
D000818:Animals D020520:Brain Infarction D002545:Brain Ischemia D002540:Cerebral Cortex D038362:Glycogen Synthase Kinase 3 D000071679:Glycogen Synthase Kinase 3 beta D007249:Inflammation D016753:Interleukin-10 D008297:Male D018696:Neuroprotective Agents D051059:PTEN Phosphohydrolase D019869:Phosphatidylinositol 3-Kinases D051057:Proto-Oncogene Proteins c-akt D017207:Rats, Sprague-Dawley D015398:Signal Transduction D020521:Stroke D014409:Tumor Necrosis Factor-alpha D017968:Vanadium Compounds
Bisperoxovanadium (Bpv) Middle cerebral artery occlusion (MCAO) Akt Ischemic stroke (GSK-3β) Glycogen synthase kinase 3β Phosphatidylinositol 3-kinase (PI3K)