title: Administration of a PTEN inhibitor BPV(pic) attenuates early brain injury via modulating AMPA receptor subunits after subarachnoid hemorrhage in rats.
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 (0.2mg/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.
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China. Electronic address: shelley_lz@aliyun.com.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China. Electronic address: fenghua8888@vip.163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000517:prevention & control; D016923:Cell Death / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors*; D021122:Protein Subunits / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D009942:Organometallic Compounds; D021122:Protein Subunits; D018091:Receptors, AMPA; C119540:oxodiperoxo(pyridine-2-carboxylate)vanadate(V); D051059:PTEN Phosphohydrolase
keywords: AMPA receptor; BPV(pic); Early brain injury; PTEN; Subarachnoid hemorrhage