Induction of vascular endothelial growth factor receptors and phosphatidylinositol 3’-kinase/Akt signaling by global cerebral ischemia in the rat

K. L. Jin, X. O. Mao, T. Nagayama, P. C. Goldsmith, D. A. Greenberg

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Vascular endothelial growth factor is an angiogenic peptide that binds to tyrosine kinase receptors on target cells to activate signal transduction pathways involving phosphatidylinositol 3’-kinase and the serine-threonine protein kinase, Akt. To determine whether this signaling pathway is activated in cerebral ischemia, we examined the expression of vascular endothelial growth factor receptors 1 and 2, and phosphatidylinositol 3’-kinase-activated phospho-Akt, in the cerebral cortex and hippocampus following transient global cerebral ischemia in the rat. Western blot analysis and immunocytochemistry demonstrated induction of vascular endothelial growth factor receptor 1 and 2 expression, and of anti-phosphatidylinositol 3’-kinase-immunoprecipitated phospho-Akt, in vulnerable regions of the cortex and hippocampus after 15min of global ischemia and 4-72h of reperfusion.These findings demonstrate that vascular endothelial growth factor receptors and receptor-coupled signal transduction pathways are induced in ischemic brain in vivo, and could therefore participate in endogenous neuroprotective responses to ischemia.

Original languageEnglish
Pages (from-to)713-717
Number of pages5
Issue number4
Publication statusPublished - 11 Oct 2000



  • Angiogenesis
  • Cerebral cortex
  • Hippocampus
  • Hypoxia
  • Signal transduction
  • Stroke

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