ABSTRACT
The brain of most vertebrates is very sensitive to anoxia. In the absence of oxygen, the mammalian brain is unable to match its ATP consumption with anaerobic ATP production, and the resulting drop in energy charge rapidly causes a loss of ion gradients, depolarization, and a release of excitatory neurotransmitters. In contrast to the devasting effects of excitatory neurotransmitters in the anoxic mammalian brain, inhibitory neurotransmitters may play an important role in protecting the brain from anoxic damage in those few vertebrates that readily survive prolonged anoxia, notably freshwater turtles, crucian carp, and goldfish. Recent experimental evidence indicate that inhibitory amino acids like GABA, glycine, and taurine could mediate the profound depression of energy consumption displayed by anoxiatolerant vertebrates. Moreover, a release of adenosine during anoxia may promote anoxic survival by both depressing energy consumption and increasing the amount of glucose available for ATP production. A hypothesis is presented suggesting that hypoxia has been an evolutionary driving force behind the striking conservation of GABA as a major inhibitory neurotransmitter and glutamate as a major excitatory neurotransmitter in vertebrates as well as invertebrates. Finally, it is noted that anoxia-tolerant vertebrates appear to have an exceptional ability to maintain the levels of monoamine neurotransmitters during prolonged anoxia.
