Timing versus duration Determinants of anesthesia-induced developmental apoptosis in the young mammalian brain

Rapidly accumulating evidence indicates that clinically used general anesthesia causes massive, widespread neu- roapoptotic degeneration in the developing mammalian brain. Susceptibility to anesthesia-induced neurotoxicity has been documented in rats, mice, guinea pigs, primates, and in this study, piglets; in short, anesthesia-induced developmental neuroapoptosis is not species-dependent. Our findings with piglets, like those in other immature mammals, demonstrate that relatively short exposure to anesthesia is just as detrimental to species with long periods of synaptogenesis as it is to those with short periods of synaptogenesis. However, the highly reproducible findings in different species also indicate that the timing of exposure to anesthesia is critically important; that is, brain regions that are at the peak of synaptogenesis are most vulnerable even when the exposure to anesthesia is relatively brief. Because the peak of synaptogenesis is characterized by intense, highly programmed neuronal communication that is vital for the survival and proper function of immature neurons, we conclude that anesthesia causes severe distur- bances in the fine equilibrium between excitatory and inhibitory neurotransmission in the developing mammalian brain, ultimately leading to neuronal redundancy and death.