Influence of nitrous oxide on granule cell migration in the dentate gyrus of the neonatal rat

For several decades, the neurotoxicities of anesthetics to the developing brain have been reported by many researchers focusing on various phenomena such as apoptosis, neurodegeneration, electrophysiological aberrations, and behavioral abnormalities. According to these reports, signals via N-methyl-D-aspartate receptors (NMDA-r) and/or γ-aminobutyric acid type A receptors (GABA(A)-r) are implicated in the anesthetic neurotoxicity. On the other hand, during brain development, NMDA-r and GABA(A)-r are also recognized to play primary roles in neural cell migration. Therefore, anesthetics exposed in this period may influence the neural cell migration of neonates, and increase the number of hilar ectopic granule cells, which are reported to be a cause of continuous neurological deficits. To examine this hypothesis, we investigated immunohistochemically granule cell distribution in the hippocampal dentate gyrus of Wistar/ST rats after nitrous oxide (N2O) exposure. At postnatal day (P) 6, 5-bromo-2'-deoxyuridine (BrdU) was administered to label newly generated cells. Then, rats were divided into groups (n = 6 each group), exposed to 50% N2O at P7, and evaluated at P21. As a result, we found that ectopic ratios (ratio of hilar/total granule cells generated at P6) were decreased in rats at P21 compared with those at P7, and increased in N2O exposed rats for over 120 min compared with the other groups. These results suggest that 50% N2O exposure for over 120 min increases the ratios of ectopic granule cells in the rat dentate gyrus