The progression and topographic distribution of interleukin-l beta expression after permanent middle cerebral artery occlusion in the rat

The cytokine interleukin-1 (IL-1) has been implicated in the exacerbation o f ischemic damage in the brains of rodents. This study has ascertained the cellular localization and chronologic and topographic distribution of pro/m ature interleukin-1 beta (IL-1 beta) protein 0.5, 1, 2, 6, 24, and 48 hours after ischemia by subjecting rats to permanent unilateral occlusion of the middle cerebral artery. Interleukin-1 beta was localized immunocytochemica lly in vibratome sections of perfusion-fixed brains. The cells that express ed IL-1 beta had the morphologic features of microglia and macrophages. Int erleukin-1 beta was first detected 1 hour after occlusion in ipsilateral me ningeal macrophage-like cells. By 6 hours, pro/mature IL-1 beta-immunoreact ive (IL-1 beta ir) putative microglia were present in the ischemic cerebral cortex, corpus callosum, caudoputamen, and surrounding tissue. By 24 and 4 8 hours after ischemia, the number and spread of IL-1 beta ir cells increas ed greatly, including those resembling activated microglia and macrophages, as the core of the infarct became infiltrated. Inrerleukin-1 beta ir cells also were present in apparently undamaged tissue, adjacent to the lesion i psilaterally, and contralaterally in the cerebral cortex, dorsal corpus cal losum, dorsal caudoputamen, and hippocampus. These results support the func tional role of IL-1 in ischemic brain damage and reveal a distinct temporal and spatial expression of IL-1 beta protein in cells believed to be microg lia and macrophages.