Dexmedetomidine Pre-Treatment of Neonatal Rats Prevents Sevoflurane-Induced Deficits in Learning and Memory in the Adult Animals

Anesthetics have been shown to cause cytotoxicity, cell death, affect neuronal growth and connectivity in animal models; however, their effects on learning and memory remain to be fully defined. Here, we examined the effects of the inhalation anesthetic sevoflurane (SEV)-both in vivo by examining learning and memory in freely behaving animals, and in vitro using cultured neurons to assess its impact on viability, mitochondrial structure, and function. We demonstrate here that neonatal exposure to sub-clinically used concentrations of SEV results in significant, albeit subtle and previously unreported, learning and memory deficits in adult animals. These deficits involve neuronal cell death, as observed in cell culture, and are likely mediated through perturbed mitochondrial structure and function. Parenthetically, both behavioural deficits and cell death were prevented when the animals and cultured neurons were pre-treated with the anesthetic adjuvant Dexmedetomidine (DEX). Taken together, our data provide direct evidence for sevoflurane-induced cytotoxic effects at the neuronal level while perturbing learning and memory at the behavioural level. In addition, our data underscore the importance of adjuvant agents such as DEX that could potentially counter the harmful effects of commonly used anesthetic agents for better clinical outcomes.

Automated summary

Anesthetics, specifically sevoflurane, have been found to have cytotoxic effects and impact neuronal growth and connectivity. In this study, the researchers observed learning and memory deficits in animals exposed to sub-clinically used concentrations of sevoflurane, which were accompanied by neuronal cell death and perturbed mitochondrial structure and function. The study also showed that these deficits and cell death could be prevented by pre-treating the animals and cultured neurons with the anesthetic adjuvant dexmedetomidine (DEX). Overall, the findings provide direct evidence for sevoflurane-induced cytotoxic effects on neurons and the negative impact on learning and memory, highlighting the importance of adjuvant agents like DEX to mitigate the harmful effects of commonly used anesthetics.