Abstract 1223 Sevoflurane disrupts the REDD1/14-3-3 Interaction and BNIP3/Rheb Binding to Allow for Continued mTOR pathway activation, Neuronal Hyperpolarization, and Cellular Protection during Periods of Hypoxia

Many surgical situations such as craniectomy can make the brain susceptible to hypoxic injury, which can lead to reduced ATP production and failure of the Na+/K+ pump. As such, there is hypoxic depolarization of the neuron, which has prominent neurotoxic effects. A recent study suggests that the anesthetic agent sevoflurane leads to activation of the mTOR pathway, increasing the synthesis of Protein Kinase M zeta (PKMz). This enhances the activity of ATP-sensitive potassium (KATP) channels and induces a sustained hyperpolarization that protects against the adverse effects of hypoxia on neural tissue.