TY - JOUR
T1 - Administration of a PTEN inhibitor BPV(pic) attenuates early brain injury via modulating AMPA receptor subunits after subarachnoid hemorrhage in rats
AU - Chen, Yujie
AU - Luo, Chunxia
AU - Zhao, Mingyue
AU - Li, Qiang
AU - Hu, Rong
AU - Zhang, John H.
AU - Liu, Zhi
AU - Feng, Hua
N1 - Publisher Copyright:
© 2015 Elsevier Ireland Ltd.
PY - 2015/2/19
Y1 - 2015/2/19
N2 - 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.
AB - 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.
KW - AMPA receptor
KW - BPV(pic)
KW - Early brain injury
KW - PTEN
KW - Subarachnoid hemorrhage
KW - PTEN Phosphohydrolase/antagonists & inhibitors
KW - Receptors, AMPA/metabolism
KW - Blood-Brain Barrier/metabolism
KW - Male
KW - Neurons/drug effects
KW - Rats, Sprague-Dawley
KW - Brain/drug effects
KW - Animals
KW - Protein Subunits/metabolism
KW - Brain Edema/prevention & control
KW - Cell Death/drug effects
KW - Organometallic Compounds/pharmacology
KW - Subarachnoid Hemorrhage/drug therapy
UR - http://www.scopus.com/inward/record.url?scp=84920869467&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84920869467&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/55b19cc3-8dd6-3dbc-a057-484c2cda6cae/
U2 - 10.1016/j.neulet.2015.01.005
DO - 10.1016/j.neulet.2015.01.005
M3 - Article
C2 - 25575796
SN - 0304-3940
VL - 588
SP - 131
EP - 136
JO - Neuroscience Letters
JF - Neuroscience Letters
ER -