Through many experimental
brain ischemia studies, it has been 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 symposium, first we 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. Next, we 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 in relation to their pathophysiological roles in the ischemic brain. Finally, we reviewed the important pathogenic roles of endoplasmic reticulum (ER) stress as well as adaptive responses of
ubiquitin-
proteasome system in
ischemia-induced neuronal cell death. 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.