Seok Joon Won, Doo Yeon Kim^† and Byoung Joo Gwag^*

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 ^†Genetics and Aging Research Unit, Massachusetts General Hospital East, Building 114, Room 3012, 114 16th Street, Charlestown, MA 02129

^*To whom correspondence should be addressed.

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.

Keywords: Glutamate, Oxidative stress, Apoptosis, Ischemia, Necrosis