title: Involvement of IL-1beta 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 TNFalpha and IL-1beta was studied by looking at the release of these cytokines in brain. The results of the present study showed an increase in IL-1beta release in cerebral cortex after exposure to acute stress. Brain levels of IL-1beta are also higher in previously stressed MCAO rats than in MCAO animals without stress. Pharmacological blockade of IL-1beta with an antibody anti-IL-1beta 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-1beta, but not TNFalpha, accounts at least partly for the worsening of MCAO consequences in brain of rats exposed to acute stress.
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid (UCM), 28040 Madrid, Spain.
authors.forename: Javier R
authors.initials: JR
authors.lastname: Caso
authors.forename: María A
authors.initials: MA
authors.lastname: Moro
authors.forename: Pedro
authors.initials: P
authors.lastname: Lorenzo
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lizasoain
authors.forename: Juan C
authors.initials: JC
authors.lastname: Leza
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D001522:Behavior, Animal; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D007276:Injections, Intraventricular / Q000379:methods; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009460:Neurologic Examination; D051381:Rats; D011916:Rats, Inbred F344; D013315:Stress, Psychological / Q000503:physiopathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000906:Antibodies; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D003345:Corticosterone