Involvement of src-kinase activation in ischemic preconditioning induced protection of mouse brain

Abstract

Aims: To investigate the role of src-kinase in ischemic preconditioning induced reversal of ischemia and reperfusion induced cerebral injury in mice.

Main methods: Bilateral carotid artery occlusion of 17min followed by reperfusion for 24h was employed to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining using both by volume and by weight methods differently. Memory was evaluated using elevated plus maze test. Rota rod test was employed to assess motor incoordination.

Key findings: Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1min and reperfusion of 1min (ischemic preconditioning) prevented markedly ischemia-reperfusion-induced cerebral injury measured in terms of infarct size (38.5±1.3% and 38.5±2.9% mean infarct of control animals was reduced to 24.3±1.2% and 23.5±1.8% of the preconditioning groups respectively), loss of memory (72.2±3.6 mean transfer latency time of control animals was reduced to 25.6±5.2 of the preconditioning group respectively) and motor coordination (78.3±17.6s mean falling down latency time of control animals was increased to a mean value of 180.9±6.5s of the preconditioning groups respectively). SU6656 (2mg/kg, ip) and PP1 (0.1mg/kg, ip), highly selective src-kinase inhibitors, attenuated this neuroprotective effect of ischemic preconditioning.

Significance: Therefore, neuroprotective effect of ischemic preconditioning may be due to src-kinase linked mechanism.