Sevoflurane Exposure Induces Neuronal Injury and Disturbs Myelin development During the Susceptible Phase in Neonatal Mice

Abstract Sevoflurane is one of the most commonly used general anesthetics for infants and young children, and previous basic research has reported that multiple or prolonged exposures with sevoflurane may affect brain development in infants and young children. However, the specific mechanism has not been well studied. We investigated whether sevoflurane would cause impaired myelin development and neuronal damage via the γ-aminobutyric acid A receptors (GABAAR) and Na+-K+-2Cl− cotransporter (NKCC1). On postnatal days 5–7, mice were each exposed to 3% sevoflurane for 2 h. Administration of the GABAAR inhibitor bicuculline and the NKCC1 inhibitor bumetanide was performed 1 h before sevoflurane treatment. On postnatal day 14, we observed that multiple sevoflurane exposures resulted in decreased levels of neurofilament protein expression and increased neuronal apoptosis. The levels of myelin-associated protein and oligodendrocyte marker were significantly reduced. At the same time myelin thickness becomes thinner. Further studies showed that bicuculline and bumetanide enhanced remyelination by inhibiting GABAAR and NKCC1 and the number of apoptotic neurons was significantly reduced. Taken together, our results indicate that sevoflurane enhances GABAAR/NKCC1 signaling, leading to neuronal damage, disturbs myelin development, and a decrease in the amount of BDNF expressed.