The mechanism of neuronal resistance and adaptation to hypoxia

Abstract

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 Ca 2+ transport modulator, in attenuating Ca 2+ 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 Ca 2+ accumulation. The sulfurcontaining 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.

Involvement of Caspase-3 in Cell Death after Hypoxia–Ischemia Declines during Brain Maturation

“…Thus, the authors adjusted the duration of HI in the different age groups to produce similar brain damage in rats of different ages according to the data presented in previous publications (Schurr and Rigor, 1987;Blumenfeld et aI., 1992;Towfighi et aI. , 1997;Towfighi and Mauger, 1998).…”

Rapid Preconditioning Protects Rats against Ischemic Neuronal Damage after 3 but Not 7 Days of Reperfusion following Global Cerebral Ischemia

“…L, left hemisphere; R, right hemisphere, Lat, lateral subsection of the CA 1 subfield of the hippocampus; Mid, middle subsection of the CA1 subfield of the hippocam pus; Med, medial subsection of the CA1 subfield of the hippo campus; Ctx, lateral cortex .• ,p < 0.05. against acute ischemic neuronal damage in the CA 1 hippocampal subfield and neocortex. The rapid in duction of IPC shown to be possible in intact brain was seen earlier in brain slices (Schurr et aI., 1986;Schurr and Rigor, 1987;Perez-Pinz6n et a!., 1996) when latencies between conditioning and test insults ranged from 30 min to 2 h. In contrast to the neuroprotection achieved by this rapid preconditioning paradigm, multiple ischemic insults separated by short periods worsened ischemic injury (Lin et aI., 1992;Lin et aI., 1993). However, both paradigms differed in that, in the mUltiple insult ischemic paradigm, insults were repeated more than twice and each insult was of the same duration.…”

Hypotaurine and sulfhydryl-containing antioxidants reduce H2S toxicity in erythrocytes from a marine invertebrate

“…HT is an effective hydroxyl radical scavenger in mammalian cells in vitro (Aruoma et al, 1988), and HT and its precursors, including cysteamine, cysteinesulphinic acid and cysteic acid, have been proposed to act as antioxidants in mammalian brain, male reproductive tissue and liver cells (Aruoma et al, 1988;Donnelly et al, 2000;Fellman and Roth, 1985;Huxtable, 1992;Schurr and Rigor, 1987). Therefore, HT may reduce sulfide toxicity by scavenging free radicals produced from sulfide oxidation.…”