The mechanism of neuronal resistance and adaptation to hypoxia.
In this work we provide a theoretical explanation for the observations that: (i) young animals are more resistant to hypoxia than adult ones and (ii) repeated exposure to a hypoxic insult increases the tolerance of young animals and isolated brain tissue to that insult. Considered here is the role of taurine, a putative Ca2+ transport modulator, in attenuating Ca2+ influx and overload in brain tissue upon hypoxia. It is proposed that the higher resistance of young animals to hypoxia stems from their higher brain content of taurine as compared with adults. The increased resistance to lack of oxygen upon re-exposure to hypoxia may occur as a result of protein and coenzyme A (CoA) breakdown which leads to the accumulation of products like cystine, cysteine, cysteamine and other sulfur-containing compounds. Upon reoxygenation, these compounds are oxidized to form taurine, which in turn attenuates neuronal Ca2+ accumulation. The sulfur-containing compounds are considered to be natural scavengers of oxygen-derived free radicals which are formed upon reoxygenation and have been implicated as a major component in the process leading to ischemic/hypoxic brain damage. Repeated hypoxic insults bring about the formation of higher levels of taurine and hence the observed adaptation to oxygen lack. The hypothesis presented here is supported by experimental observations in our laboratory and those of others.
Schurr
A
A
Department of Anesthesiology, University of Louisville School of Medicine, KY 40292.
Rigor
B M
BM
D000222:Adaptation, Physiological; D000367:Age Factors; D000603:Amino Acids, Sulfur / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000254:growth & development / Q000502:physiology; D001923:Brain Chemistry; D002118:Calcium / Q000378:metabolism; D003065:Coenzyme A / Q000378:metabolism; D005609:Free Radicals; D000860:Hypoxia / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology; D008954:Models, Biological; D009474:Neurons / Q000502:physiology*; D013654:Taurine / Q000096:biosynthesis / Q000502:physiology
D000603:Amino Acids, Sulfur; D005609:Free Radicals; D013654:Taurine; D003065:Coenzyme A; D002118:Calcium