Administration of a PTEN inhibitor BPV(pic) attenuates early brain injury via modulating AMPA receptor subunits after subarachnoid hemorrhage in rats

Yujie Chen, Chunxia Luo, Mingyue Zhao, Qiang Li, Rong Hu, John H. Zhang, Zhi Liu, Hua Feng

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of this study was to investigate whether the phosphatase and tensin homolog deleted on chromosome ten (PTEN) inhibitor dipotassium bisperoxo(pyridine-2-carboxyl) oxovanadate (BPV(pic)) attenuates early brain injury by modulating α-amino-3-hydroxy-5-methyl-4-isoxa-zolep-propionate (AMPA) receptor subunits after subarachnoid hemorrhage (SAH). A standard intravascular perforation model was used to produce the experimental SAH in Sprague-Dawley rats. BPV(pic) treatment (0.2. mg/kg) was evaluated for effects on neurological score, brain water content, Evans blue extravasation, hippocampal neuronal death and AMPA receptor subunits alterations after SAH. We found that BPV(pic) is effective in attenuating BBB disruption, lowering edema, reducing hippocampal neural death and improving neurological outcomes. In addition, the AMPA receptor subunit GluR1 protein expression at cytomembrane was downregulated, whereas the expression of GluR2 and GluR3 was upregulated after BPV(pic) treatment. Our results suggest that PTEN inhibited by BPV(pic) plays a neuroprotective role in SAH pathophysiology, possibly by alterations in glutamate AMPA receptor subunits.

Original languageEnglish
Pages (from-to)131-136
Number of pages6
JournalNeuroscience Letters
Volume588
DOIs
StatePublished - Feb 19 2015

ASJC Scopus Subject Areas

  • General Neuroscience

Keywords

  • AMPA receptor
  • BPV(pic)
  • Early brain injury
  • PTEN
  • Subarachnoid hemorrhage
  • PTEN Phosphohydrolase/antagonists & inhibitors
  • Receptors, AMPA/metabolism
  • Blood-Brain Barrier/metabolism
  • Male
  • Neurons/drug effects
  • Rats, Sprague-Dawley
  • Brain/drug effects
  • Animals
  • Protein Subunits/metabolism
  • Brain Edema/prevention & control
  • Cell Death/drug effects
  • Organometallic Compounds/pharmacology
  • Subarachnoid Hemorrhage/drug therapy

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