EXACERBATION OF ISCHEMIC BRAIN-DAMAGE BY LOCALIZED STRIATAL INJECTIONOF INTERLEUKIN-1-BETA IN THE RAT

Interleukin-1 beta (IL-1 beta) has been implicated in ischemic brain d amage. The site of action of IL-1 beta in such damage is not known, bu t we have demonstrated previously that injection of the interleukin-1 receptor antagonist (IL-1ra) in the striatum but not the cortex of rat s inhibits damage caused by permanent middle cerebral artery occlusion . The present study investigated the site of action of IL-1 beta on is chemic damage by examining the effects of intracerebroventricular, str iatal, or cortical injection of recombinant IL-1 beta at the onset of permanent middle cerebral artery occlusion in the rat. Intracerebroven tricular injection of IL-1 beta (2.5 ng) significantly increased infar ct volume in the striatum (35%, P < 0.0001) and in the cortex (44%, P < 0.0001) compared with vehicle treatment. Direct injection of IL-1 be ta into the striatum also increased infarct volume in both the striatu m (36%, P < 0.0001) and the cortex (38%, P < 0.0001), whereas injectio n of IL-1 beta into the cortex failed to affect infarct volume in eith er the striatum or the cortex. Cortical injection of a higher dose of IL-1 beta (20 ng) also failed to affect ischemic damage in either the striatum or the cortex. Injection of IL-1 beta into the striatum contr alateral to the infarction had no effect on striatal damage in the isc hemic hemisphere, but did increase cortical damage by 18% (P < 0.0001) . In separate groups of animals, IL-1 beta (2.5 ng) was injected into either the striatum or the cortex, and body temperature was recorded c ontinuously in conscious free-moving animals by remote telemetry. Inje ction of IL-1 beta at either site failed to influence body temperature , suggesting that exacerbation of brain damage by striatal injection o f IL-1 beta is not caused by effects on body temperature. These result s imply that IL-1 beta exacerbates ischemic damage by specific actions in the striatum where it can influence damage at distant sites in the cortex.