Exacerbation of ischemic brain damage by localized striatal injection of interleukin-1beta in the rat.
Interleukin-1beta (IL-1beta) has been implicated in ischemic brain damage. The site of action of IL-1beta in such damage is not known, but we have demonstrated previously that injection of the interleukin-1 receptor antagonist (IL-1ra) in the striatum but not the cortex of rats inhibits damage caused by permanent middle cerebral artery occlusion. The present study investigated the site of action of IL-1beta on ischemic damage by examining the effects of intracerebroventricular, striatal, or cortical injection of recombinant IL-1beta at the onset of permanent middle cerebral artery occlusion in the rat. Intracerebroventricular injection of IL-1beta (2.5 ng) significantly increased infarct volume in the striatum (35%, P < 0.0001) and in the cortex (44%, P < 0.0001) compared with vehicle treatment. Direct injection of IL-1beta into the striatum also increased infarct volume in both the striatum (36%, P < 0.0001) and the cortex (38%, P < 0.0001), whereas injection of IL-1beta into the cortex failed to affect infarct volume in either the striatum or the cortex. Cortical injection of a higher dose of IL-1beta (20 ng) also failed to affect ischemic damage in either the striatum or the cortex. Injection of IL-1beta into the striatum contralateral to the infarction had no effect on striatal damage in the ischemic hemisphere, but did increase cortical damage by 18% (P < 0.0001). In separate groups of animals, IL-1beta (2.5 ng) was injected into either the striatum or the cortex, and body temperature was recorded continuously in conscious free-moving animals by remote telemetry. Injection of IL-1beta at either site failed to influence body temperature, suggesting that exacerbation of brain damage by striatal injection of IL-1beta is not caused by effects on body temperature. These results imply that IL-1beta exacerbates ischemic damage by specific actions in the striatum where it can influence damage at distant sites in the cortex.
School of Biological Sciences, University of Manchester, United Kingdom.
R P
RP
Stroemer
N J
NJ
Rothwell
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology*; D002544:Cerebral Infarction / Q000473:pathology* / Q000503:physiopathology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D007839:Functional Laterality; D006801:Humans; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000633:toxicity; D013238:Stereotaxic Techniques
D007375:Interleukin-1; D011994:Recombinant Proteins