Won Seok Joon, Kim Doo Yeon, Gwag Byoung Joo
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.
J Biochem Mol Biol. 2002 Jan 31;35(1):67-86. doi: 10.5483/bmbrep.2002.35.1.067.
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.
已确定在生理和病理条件下引发神经元死亡的三种途径。离子型谷氨酸受体的过度激活会导致Ca2+和Na+的流入和积累，从而导致神经元在数小时内迅速肿胀并随后死亡。第二条途径是由活性氧和氮物质的积累导致的氧化应激引起的。在发育过程中经常发生的凋亡或程序性细胞死亡已被认为是成熟神经系统中病理性神经元死亡的另一条途径。越来越多的证据表明，兴奋性毒性、氧化应激和凋亡通过独特且相互排斥的信号转导途径传播，并导致缺氧缺血性脑损伤后的神经元丢失。因此，缺氧缺血性神经元损伤的治疗干预应旨在协同预防兴奋性毒性、氧化应激和凋亡。
