Clinical perspectives: neuroprotection lessons from hypoxia-tolerant organisms.
An effective treatment for brain ischemia is a pressing medical need. Research on brain ischemia has largely focused on understanding the mechanisms of neuron death as a way of identifying targets for therapy. An attractive alternative approach is to identify the survival strategies of hypoxia-tolerant neurons. The adaptation of vertebrate neurons to hypoxia occurs in at least three major ways: (1) as a constitutive property of neurons in anoxia-tolerant turtles and fish, (2) as a property of intra-uterine and early post-natal mammalian development, and (3) as part of a slower, chronic process, as in acclimitization to high altitude. Research on hypoxia-tolerant neurons has already revised several earlier concepts, including the role of calcium in cell death and survival, and the value of N-methyl-d-aspartate (NMDA) receptor antagonism. A broad and fundamental understanding of how neurons adapt to hypoxia is likely to help guide efforts to find new treatments for brain hypoxia and ischemia.
Department of Anesthesia, University of California, San Francisco, CA 94143-0542, USA.
Philip E
PE
Bickler
D000064:Acclimatization / Q000502:physiology; D000222:Adaptation, Physiological; D000531:Altitude; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D005399:Fishes / Q000378:metabolism*; D008322:Mammals / Q000196:embryology / Q000378:metabolism*; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014426:Turtles / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D010100:Oxygen; D002118:Calcium