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 intrauterine 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.