Bradykinin preconditioning induces protective effects against focal cerebral ischemia in rats

Bradykinin is recognized to play an important role in heart ischemia tolerance, and it is expressed in ischemic brain. We hypothesized that bradykinin might play a role in the regulation of tolerance to ischemic brain when administered prior to the ischemic episode. We investigated the effects of bradykinin preconditioning on ischemic damage using an in vivo model of 2-h ischemic and 24-h reperfusion focal cerebral ischemia in rats. Prior to ischemia, bradykinin was pumped into the brain via external carotid artery at a dose of 10 mu g/kg/min for 15 min. A significant reduction of 41.20% in infarct size was noted in rats pretreated by bradykinin 15 min prior to ischemia. Brain edema and permeability of blood-brain barrier were also decreased. Immunohistochemical and Western blot analysis of brains revealed a significant increase in basic fibroblast growth factor protein levels. The study demonstrated that bradykinin preconditioning induces protection against ischemic brain injury, and this protection is likely due to the protection of cerebral vasculature and the promotion of neuronal survival. (c) 2005 Elsevier B.V. All rights reserved.