Alleviating brain stress: what alternative animal models have revealed about therapeutic targets for hypoxia and anoxia

Abstract

While the mammalian brain is highly dependent on oxygen, and can withstand only a few minutes without air, there are both vertebrate and invertebrate examples of anoxia tolerance. One example is the freshwater turtle, which can withstand days without oxygen, thus providing a vertebrate model with which to examine the physiology of anoxia tolerance without the pathology seen in mammalian ischemia/reperfusion studies. Insect models such as Drosophila melanogaster have additional advantages, such as short lifespans, low cost and well-described genetics. These models of anoxia tolerance share two common themes that enable survival without oxygen: entrance into a state of deep hypometabolism, and the suppression of cellular injury during anoxia and upon restoration of oxygen. The study of such models of anoxia tolerance, adapted through millions of years of evolution, may thus suggest protective pathways that could serve as therapeutic targets for diseases characterized by oxygen deprivation and ischemic/reperfusion injuries.