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Treatment with sodium orthovanadate reduces blood–brain barrier disruption via phosphatase and tensin homolog deleted on chromosome 10 (PTEN) phosphorylation in experimental subarachnoid hemorrhage
Author(s) -
Hasegawa Yu,
Suzuki Hidenori,
Altay Orhan,
Chen Hank,
Zhang John H.
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22801
Subject(s) - tensin , pten , phosphorylation , phosphatase , sodium orthovanadate , subarachnoid hemorrhage , cancer research , chemistry , microbiology and biotechnology , medicine , biology , biochemistry , pi3k/akt/mtor pathway , signal transduction
Attenuation of blood–brain barrier (BBB) disruption is one of the therapeutic candidates for treatment of subarachnoid hemorrhage (SAH). In this study, the protective effect of sodium orthovanadate (SOV) on BBB disruption was investigated in SAH using the endovascular perforation model. Fifty‐five rats were randomly assigned to sham‐operated, SAH treated with saline (as a vehicle), or 10 mg/kg SOV groups and were evaluated for neurofunction and Evans blue dye extravasation. The phosphorylation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and mitogen‐activated protein kinase (MAPK) and the expression of matrix metalloproteinase‐9 (MMP‐9), occludin, and collagen‐IV were examined by Western blot analyses. Cell death among endothelial cells was revealed by immunofluorescence and terminal deoxynucleotidyl transferase‐mediated uridine 5′‐triphosphate‐biotin nick end‐labeling staining. SOV significantly improved neurofunction and reduced Evans blue dye extravasation in brains after SAH. SOV phosphorylated PTEN, decreased phospho‐JNK and MMP‐9, and preserved occludin expression. SOV also attenuated SAH‐induced capillary endothelial cell death. The current study showed that SOV was protective against BBB disruption after SAH, possibly via PTEN phosphorylation. © 2011 Wiley Periodicals, Inc.