Toxicol Sci 2016 Jan 30;149(1):121-33. Epub 2015 Sep 30.
*Center for Brain Repair and Rehabilitation, University of Gothenburg, Gothenburg, SE-40530, Sweden; *Center for Brain Repair and Rehabilitation, University of Gothenburg, Gothenburg, SE-40530, Sweden;
The possibility that exposure to general anesthetics during early life results in long-term impairment of neural function attracted considerable interest over the past decade. Extensive laboratory data suggest that administration of these drugs during critical stages of central nervous system development can lead to cell death, impaired neurogenesis, and synaptic growth as well as cognitive deficits. These observations are corroborated by several recent human epidemiological studies arguing that such cognitive impairment might also occur in humans. Despite the potential public health importance of this issue, several important questions remain open. Amongst them, how the duration of anesthesia exposure impact on outcome is as yet not fully elucidated. To gain insight into this question, here we focused on the short- and long-term impact of a 30-min-long exposure to clinically relevant concentrations of sevoflurane in rat pups at 2 functionally distinct stages of the brain growth spurt. We show that this treatment paradigm induced developmental stage-dependent and brain region-specific acute but not lasting changes in dendritic spine densities. Electrophysiological recordings in hippocampal brain slices from adult animals exposed to anesthesia in the early postnatal period revealed larger paired-pulse facilitation but no changes in the long-term potentiation paradigm when compared with nonanesthetized controls. 5-bromo-2-deoxyuridine pulse and pulse-chase experiments demonstrated that neither proliferation nor differentiation and survival of hippocampal progenitors were affected by sevoflurane exposure. In addition, behavioral testing of short- and long-term memory showed no differences between control and sevoflurane-exposed animals. Overall, these results suggest that brief sevoflurane exposure during critical periods of early postnatal development, although it does not seem to exert major long-term effects on brain circuitry development, can induce subtle changes in synaptic plasticity and spine density of which the physiological significance remains to be determined.