Cellular and molecular pathways of ischemic neuronal death.
Three routes have been identified triggering neuronal death under physiological and pathological conditions. Excess activation of ionotropic glutamate receptors cause influx and accumulation of Ca2+ and Na+ that result in rapid swelling and subsequent neuronal death within a few hours. The second route is caused by oxidative stress due to accumulation of reactive oxygen and nitrogen species. Apoptosis or programmed cell death that often occurs during developmental process has been coined as additional route to pathological neuronal death in the mature nervous system. Evidence is being accumulated that excitotoxicity, oxidative stress, and apoptosis propagate through distinctive and mutually exclusive signal transduction pathway and contribute to neuronal loss following hypoxic-ischemic brain injury. Thus, the therapeutic intervention of hypoxic-ischemic neuronal injury should be aimed to prevent excitotoxicity, oxidative stress, and apoptosis in a concerted way.
Won
Seok Joon
SJ
Center for the Interventional Therapy of Stroke and Alzheimers Disease, Department of Pharmacology, Ajou University School of Medicine, San 5, Wonchondong, Paldalgu, Suwon, Kyungkido 442-749, South Korea.
Kim
Doo Yeon
DY
Gwag
Byoung Joo
BJ
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D016718:Arachidonic Acid / Q000378:metabolism; D001921:Brain / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D005609:Free Radicals; D006801:Humans; D000860:Hypoxia; D007511:Ischemia / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008928:Mitochondria / Q000473:pathology; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D010741:Phospholipases A / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D000975:Antioxidants; D005609:Free Radicals; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D019014:fas Receptor; D016718:Arachidonic Acid; D012964:Sodium; D010741:Phospholipases A; D002118:Calcium