The relevance of ischemic preconditioning and tolerance in the neuroprotectivity of ischemia-induced neuronal damage: an up-to-date review

The purpose of this review is to describe the progress made to date in the search for an efficient and long-lasting neuroprotectivity to reduce the se quelae of ischemia- and reperfusion-induced damage of the nervous tissue. S everal neuroprotective adjuncts have been studied and, among them, ischemic tolerance was found as one possible therapeutic approach, at least for som e experimental paradigms. Several experimental models that help to stimulat e ischemic preconditioning and ischemic tolerance such as global-global, gl obal-focal, focal-global and focal-focal models were investigated and found be efficient at least in some postischemic periods. While these previous m odels proved to be efficient with regard to longer survival time, new exper imental models that help to provoke almost immediate tolerance were discove red quite recently. Several factors were found among the possible pathophys iological and molecular mechanisms forming the basis of ischemic tolerance. These factors were the modifications of the glutamate release, the activat ion of adenosine and its corresponding receptors, the appearance of newly a nd abruptly formed proteins, and mainly heat shock proteins. Quite recently , some highly specialized proteins were discovered acting on interleukin Ip receptor site.