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: Lun-Lin Mao, Dong-Lin Hao, Xiao-Wei Mao, Yuan-Feng Xu, Ting-Ting Huang, Bo-Na Wu, Li-Hui Wang
• Journal: Neuroscience letters (Neurosci Lett) Vol. 602 Pg. 120-5 (Aug 18 2015) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 26141612 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Neuroprotective Agents
• Tumor Necrosis Factor-alpha
• Vanadium Compounds
• bisperoxovanadium
• Interleukin-10
• Phosphatidylinositol 3-Kinases
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, rat
• Proto-Oncogene Proteins c-akt
• Glycogen Synthase Kinase 3
• PTEN Phosphohydrolase
• Pten protein, rat

Topics

• Animals
• Brain Infarction (drug therapy, metabolism, pathology)
• Brain Ischemia (drug therapy, metabolism)
• Cerebral Cortex (drug effects, metabolism, pathology)
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Inflammation (drug therapy, metabolism)
• Interleukin-10 (metabolism)
• Male
• Neuroprotective Agents (therapeutic use)
• PTEN Phosphohydrolase (antagonists & inhibitors, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats, Sprague-Dawley
• Signal Transduction
• Stroke (drug therapy, metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• Vanadium Compounds (therapeutic use)