Involvement of IL-1β in acute stress-induced worsening of cerebral ischaemia in rats

Abstract

Stress is known to be one of the risk factors of stroke. Most of the knowledge on the effects of stress on cerebrovascular disease in humans is restricted to catecholamines and glucocorticoids effects on blood pressure and/or development of atherosclerosis. However, few experimental studies have examined the possible mechanisms by which stress may affect stroke outcome. We have used an acute stress protocol consisting of the exposure of male Fischer rats to an acute, single exposure immobilisation protocol (6 h) prior to permanent middle cerebral artery occlusion (MCAO), and we have found that stress worsens behavioural and neurological outcomes and increased infarct size after MCAO. The possible regulatory role of the TNFα and IL-1β was studied by looking at the release of these cytokines in brain. The results of the present study showed an increase in IL-1β release in cerebral cortex after exposure to acute stress. Brain levels of IL-1β are also higher in previously stressed MCAO rats than in MCAO animals without stress. Pharmacological blockade of IL-1β with an antibody anti-IL-1β led to a decrease in the infarct size as well as in neurological and behavioural deficits after MCAO. In summary, our results indicate that IL-1β, but not TNFα, accounts at least partly for the worsening of MCAO consequences in brain of rats exposed to acute stress.