Treatment with sodium orthovanadate reduces blood-brain barrier disruption via phosphatase and tensin homolog deleted on chromosome 10 (PTEN) phosphorylation in experimental subarachnoid hemorrhage

J Neurosci Res. 2012 Mar;90(3):691-7. doi: 10.1002/jnr.22801. Epub 2011 Dec 20.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / physiopathology
  • Cell Death / drug effects
  • Collagen Type IV / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Membrane Proteins / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Occludin
  • PTEN Phosphohydrolase / metabolism*
  • Permeability / drug effects
  • Phosphorylation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Subarachnoid Hemorrhage / drug therapy*
  • Subarachnoid Hemorrhage / metabolism
  • Subarachnoid Hemorrhage / physiopathology
  • Vanadates / pharmacology*
  • Vanadates / therapeutic use

Substances

  • Collagen Type IV
  • Membrane Proteins
  • Occludin
  • Ocln protein, rat
  • Vanadates
  • Mitogen-Activated Protein Kinases
  • PTEN Phosphohydrolase
  • Matrix Metalloproteinase 9