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1564818 
Journal Article 
Timing versus duration Determinants of anesthesia-induced developmental apoptosis in the young mammalian brain 
Rizzi, S; Ori, C; Jevtovic-Todorovic, V 
2010 
Yes 
Annals of the New York Academy of Sciences
ISSN: 0077-8923
EISSN: 1749-6632 
Annals of the New York Academy of Sciences 
1199 
43-51 
English 
20633108 
WOS:000282838900005 
Rapidly accumulating evidence indicates that clinically
used general anesthesia causes massive, widespread neuroapoptotic 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 disturbances in the fine equilibrium between
excitatory and inhibitory neurotransmission in the developing mammalian brain, ultimately leading
to neuronal redundancy and death. 
piglets; isoflurane; midazolam; nitrous oxide; fentanyl; synaptogenesis