Inhalation of hydrogen gas mitigates sevoflurane-induced neuronal apoptosis in the neonatal cortex and is associated with changes in protein phosphorylation.

Abstract

Sevoflurane exposure in neonatal mice induces apoptosis in neural progenitor cells of the retrosplenial cortex. Co-administration of 1–8% hydrogen gas for 3 hours reduced caspase-3-mediated apoptotic cell death and attenuated c-Jun phosphorylation along with downstream pathway activation, both of which are driven by oxidative stress. Lipid peroxidation and oxidative DNA damage elevated by anesthesia were also diminished by hydrogen inhalation. Phosphoproteomic profiling identified clusters of differentially phosphorylated proteins in the sevoflurane-exposed neonatal brain, including those involved in neuronal development and synaptic signaling. Hydrogen inhalation altered cellular transport pathways dependent on hyperphosphorylated proteins such as microtubule-associated protein family members, suggesting these changes contribute to the neuroprotective mechanism against anesthetic-induced neuronal cell death.

Mechanism

Hydrogen gas reduces oxidative stress, suppresses c-Jun phosphorylation and caspase-3-mediated apoptosis, and modifies phosphorylation of cellular transport proteins including microtubule-associated protein family members in the sevoflurane-exposed neonatal brain.