Résumés
Résumé
Les accidents ischémiques et les crises épileptiques font partie des causes majeures de mort neuronale. Malgré les nombreuses recherches sur la neuroprotection et la découverte de nouvelles molécules capables de bloquer certains des événements délétères chez l’animal, peu de traitements sont disponibles pour lutter contre la mort neuronale induite par ces maladies. Le plus efficace reste le traitement thrombolytique en phase aiguë des accidents ischémiques cérébraux, qui ne peut toutefois être administré que chez une très faible population de patients. La prévention visant à réduire l’incidence des facteurs de risque reste donc la principale stratégie thérapeutique. La tolérance cérébrale est un phénomène endogène reposant sur l’induction préventive de la résistance neuronale. La compréhension de ses mécanismes permettrait d’identifier de nouvelles cibles thérapeutiques. Les inducteurs pharmacologiques de la tolérance cérébrale devraient conduire à la même neuroprotection et à la mise en oeuvre de nouvelles thérapeutiques.
Summary
Ischemia and seizures are common diseases that result in neuronal death. To-date, there are no available treatments to block or reverse neuronal death pathways in patients who suffer from these diseases. All drugs that have been shown to be neuroprotective in animal models have failed in human trials. Therefore, the potential of preventative strategies for therapy is increasingly explored. Experimental studies have demonstrated that a brief cerebral ischemic insult, that is not harmful by itself, results in a temporary protective adaptation in the brain against a subsequent ischemic episode that would otherwise be lethal. This process, termed ischemic preconditioning, has been confirmed in different models of cerebral ischemia. A similar phenomenon observed after a mild epileptic insult conferred a transitory tolerance to a subsequent epileptic episode. This process is termed epileptic tolerance. Other stresses, like hyperthermia or spreading depression, also enhanced brain resistance to detrimental effects of ischemic or epileptic injury. Recently, a cross tolerance between ischemia and epilepsy has been reported. Also, some retrospective studies in humans suggest that endogenous ischemic preconditioning exists in the brain. Altogether these insights of brain tolerance point to the future discovery of potentially useful targets for acute neuroprotection as well as preventive therapy.
Parties annexes
Références
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