Acetyl-l-carnitine does not prevent neurodegeneration in a rodent model of prolonged neonatal anesthesia

Many studies have shown that prolonged or repeated use of general anesthesia early in life can cause an increase in neurodegeneration and lasting changes in behavior. While short periods of general anesthesia appear to be safe, there is a concern about the neurotoxic potential of prolonged or repeated general anesthesia in young children. Unfortunately, the use of general anesthesia in children cannot be avoided. It would be a great benefit to develop a strategy to reduce or reverse anesthesia mitigated neurotoxicity. The mechanisms behind anesthesia related neurotoxicity are unknown, but evidence suggests that mitochondrial dysfunction and abnormal energy utilization are involved. Recent research suggests that a class of compounds known as carnitines may be effective at preventing anesthesia related neurotoxicity by influencing fatty acid metabolism in the mitochondria. However, it is unknown if carnitines can provide protection against changes in behavior associated with early life exposure to anesthesia. Accordingly, we evaluated the neuroprotective potential of acetyl-l-carnitine in 7-day old rats. Rat pups were exposed to 6 h of general anesthesia with sevoflurane or a control condition, with and without acetyl-l-carnitine. The oxygenation level of animals was continuously monitored during sevoflurane exposure, and any animal showing signs of hypoxia was removed from the study. Animals exposed to sevoflurane showed clear signs of neurodegeneration 2 h after sevoflurane exposure. The hippocampus, cortex, thalamus, and caudate putamen all had elevated levels of Fluoro-Jade C staining. Despite the elevated levels of Fluoro-Jade C, few behavioral changes were observed in an independent cohort of animals treated with sevoflurane. Furthermore, acetyl-l-carnitine had little impact on levels of Fluoro-Jade C staining in animals treated with sevoflurane. These data suggest that acetyl-l-carnitine may offer little protection again anesthesia related neurotoxicity in fully oxygenated animals.