Sex-specific behavioral impairments and neuronal alterations in Wistar rats following repeated sevoflurane exposure during developmental stages

Abstract

Objectives: This study aimed to investigate the effects of repeated exposure to sevoflurane as an anesthetic agent during various developmental stages, namely neonatal, preadolescent, and adult, on behavioral, synaptic, and neuronal plasticity in male and female Wistar rats.

Methods: Rats were exposed to sevoflurane during three developmental stages: neonatal (PN7), pre-adolescence (PN28), and adulthood (PN90). Behavioral performance was evaluated with the Morris Water Maze. Electrophysiological analyses measured population spike (PS) amplitude, slope, and long-term potentiation (LTP) to assess synaptic plasticity. Short-term plasticity was additionally studied using paired-pulse facilitation tests.

Results: Repeated neonatal exposure to sevoflurane caused significant impairments in spatial learning and memory, whereas exposures during pre-adolescence and adulthood had minimal effects. Electrophysiological data revealed a reduction in PS amplitude and slope, as well as impaired LTP, particularly in neonatal and pre-adolescent groups, with more severe deficits observed in males. Paired-pulse facilitation indicated greater short-term plasticity deficits in males at shorter intervals.

Discussion: The findings of this study highlight the increased vulnerability of the developing brain, particularly during the neonatal period, to the adverse effects of repeated exposure to sevoflurane, resulting in long-lasting impairments in synaptic function and behavior. The results emphasize the importance of caution when administering sevoflurane to young children and suggest that early-life exposure may have lasting effects on cognitive and synaptic health.

Keywords: Sevoflurane; behavioral impairments; neonatal, pre-adolescence, synaptic plasticity; sex-specific effects; spatial memory impairment.