Abstract
Since the first documentation of the induction of heat shock protein following transient cerebral ischemia, much experimental evidence suggested that all of the cellular elements in the central nervous system show dynamic stress responses depending on the degree of environmental changes induced by ischemia and reperfusion. In this review, first 1 focused on the importance of the usage of an appropriate experimental model for brain ischemia and reperfusion, and I presented our work on mouse models of transient global and focal ischemia. Next, I reviewed the pathogenic role of microvascular stasis (i.e., secondary ischemia) caused by the primary ischemic event and demonstrated the important role of cell adhesion molecules through the experiments using ICAM-1 knock-out mouse as a model of brain ischemia/reperfusion. Thirdly, I discussed the ischemia-induced neuronal cell responses in relation to the apoptosis-like selective neuronal death and the induction of adopted stress responses including stress protein synthesis and ‘ischemic tolerance’ phenomenon. A variety of stress proteins induced by ischemic stress have been reviewed and a pivotal role of tyrosine kinase system in selective neuronal death has been suggested in the gerbil model of transient forebrain ischemia. Finally, I showed the important pathophysiological roles of glial cells such as astrocytes and oligodendrocytes in the celluar cross-talk triggered by an ischemic event. For the development of a novel therapeutic agent against ischemic stroke, it is quite important to clarify both the negative and positive cellular responses induced by brain ischemia/reperfusion.
