ABSTRACT

Growth factors including insulin-like growth factor-1 (IGF-1) promotes cell survival in ischemic brain injury. IGF-1 receptor coupled with tyrosine kinase activated phosphatidylinositol 3-kinase (PI3-K) followed by protein kinase B (Akt) in the hippocampal neurons. We here introduce a new approach of signal transduction therapy in the ischemic insult. Adult Mongolian gerbils were subjected to 5-min forebrain ischemia. Like IGF-1, intracerebroventricular injection of sodium orthovanadate, a protein tyrosine phosphatase inhibitor, 30 min before ischemia blocked delayed neuronal death in the CA1 region. The neuroprotective effects of orthovanadate and IGF-1 were associated with increased Akt activity in the CA1 region. Furthermore, we found that the activation of MAPK as well as Akt underlie the neuroprotective effects of orthovanadate on the delayed neuronal death in the CA1 region following transient forebrain ischemia. These results suggest that molecular targeting therapy for survival signaling is powerful tool in the neuroprotection for ischemic insult.