[Molecular mechanism of brain infarction].
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.
Matsumoto
Masayasu
M
Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical Sciences.
Yamashita
Hiroshi
H
Kitagawa
Kazuo
K
Kohriyama
Tatsuo
T
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000166:cytology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D003546:Cysteine Endopeptidases / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008833:Microcirculation; D009097:Multienzyme Complexes / Q000502:physiology; D018384:Oxidative Stress; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex; D025801:Ubiquitin / Q000502:physiology
D016166:Free Radical Scavengers; D006360:Heat-Shock Proteins; D009097:Multienzyme Complexes; D010975:Platelet Aggregation Inhibitors; D025801:Ubiquitin; D018799:Intercellular Adhesion Molecule-1; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex