Cognitive Impairments Induced by Repeated Sevoflurane Exposure During Pre-adolescence in Adult Male and Female Rats: Involvement of Biochemical, Histological and Neuroplasticity Approaches

Background: In some therapeutic interventions, repeated exposure to pre-adolescence anesthesia is necessary. According to research, exposure to general anesthetics during pre-adolescence can lead to cell death, cognitive and behavioral problems, and neurobehavioral difficulties as an adult. The current study aimed to provide detailed morphological and functional evaluations of the long-term impacts of repeated sevoflurane exposure in male and female rats. Materials and Methods: Seventy-two pre-adolescent rats were randomly divided into male and female control and inhaled sevoflurane groups (concentration of 2%) daily for 15 days. Animals received care for 20-30 days. The influence of repeated exposure to sevoflurane on cognitive functions was tested using the Morris Water Maze, novel object, and social interaction tests. As a measure of oxidative stress, superoxide dismutase (SOD) and glutathione levels were measured. Toluidine blue stain was utilized to evaluate the number of dark neurons in the hippocampus. Effects of sevoflurane on synaptic plasticity were compared in the performant pathway of the CA1 of the hippocampus. Results: Repeated sevoflurane exposure in pre-adolescence led to behavioral disorders in male and female adult rats; there was no significant difference in levels of superoxide dismutase and glutathione. We found a significant quantifiable increase in dark neurons. Electrophysiological recordings indicated impaired long-term potentiation and pair-pulse in adult animals that received repeat sevoflurane exposure. Conclusion: According to our findings, repeated exposure to sevoflurane during pre-adolescence can cause changes in the hippocampus and neuroplasticity in the adult brain. Results from this study may provide a new perspective on how repeated exposure to anesthesia can lead to toxic effects in pre-adolescent rats.