Neuroprotective effects of bisperoxovanadium on cerebral ischemia by inflammation inhibition

• Published in: Neuroscience letters 2015-08, Vol.602, p.120-125
• Main Authors: Mao, Lun-Lin, Hao, Dong-Lin, Mao, Xiao-Wei, Xu, Yuan-Feng, Huang, Ting-Ting, Wu, Bo-Na, Wang, Li-Hui
• Format: Article
• Language: English
• Subjects: Akt; Animals; Bisperoxovanadium (Bpv); Brain Infarction - drug therapy; Brain Infarction - metabolism; Brain Infarction - pathology; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Glycogen synthase kinase 3β; GSK-3β; Inflammation - drug therapy; Inflammation - metabolism; Interleukin-10 - metabolism; Ischemic stroke; Male; Middle cerebral artery occlusion (MCAO); Neuroprotective Agents - therapeutic use; Phosphatidylinositol 3-kinase (PI3K); Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - antagonists & inhibitors; PTEN Phosphohydrolase - metabolism; Rats, Sprague-Dawley; Signal Transduction; Stroke - drug therapy; Stroke - metabolism; Tumor Necrosis Factor-alpha - metabolism; Vanadium Compounds - therapeutic use
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2015.06.040

•Bpv demonstrates neuroprotective effects in ischemic stroke rats.•Bpv inhibits inflammation response in ischemic stroke rats.•PI3K-Akt-GSK-3β pathways may be related to inhibition of inflammation by Bpv. 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 (0.2mg/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 (0.2mg/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.