Volatile Anesthetics Transiently Disrupt Neuronal Development in Neonatal Rats

Volatile anesthetics can cause neuronal and glial toxicity in the developing mammalian brain, as well as long-termdefects in learning and memory. The goals of this study were to compare anesthetics using a clinically relevant exposure paradigm, and to assess the anesthetic effects on hippocampal development and behavior. Our hypothesis was that volatile anesthetics disrupt hippocampal development, causing neurobehavioral defects later in life. Bromodeoxyuridine (BrdU) was administered to rats on postnatal day (P) 1, and the rats were exposed to volatile anesthetics (isoflurane, sevoflurane, or desflurane) for 2h on P2. On days P7 and P14, the BrdU-labeled cells were quantified in the hippocampal dentate gyrus using immunohistochemical assays and fluorescent microscopy. Caspase-3 positive cells were quantified on P2 to evaluate apoptosis. The remaining animals underwent behavioral testing at ages 6 weeks and 6 months, using the Morris Water Maze. Significantly fewer BrdU-positive cells were detected in the hippocampal dentate gyrus in both isoflurane and desflurane-treated animals compared with controls at P7, but there were no changes in cell numbers after sevoflurane exposure. Cell counts for all three anesthetics compared with controls were equivalent at P14. Isoflurane or desflurane exposure yielded slight differences in the behavioral tests at 6 weeks, but no differences at 6 months post-exposure. We conclude that a single 2-h exposure at P2 to either isoflurane or desflurane causes a transient disruption of hippocampal neuronal development with no significant detectable long-term effects on learning and memory, whereas the same exposure to sevoflurane has no effects.