Hydrogen gas attenuates sevoflurane neurotoxicity through inhibiting nuclear factor κ-light-chain-enhancer of activated B cells signaling and proinflammatory cytokine release in neonatal rats.

Abstract

Neurotoxic effects of anesthetic agents on the developing brain represent a growing concern. Neonatal rats were exposed to sevoflurane alone or in combination with hydrogen gas for 2 hours, and cognitive performance was assessed at 10 weeks of age using Y-maze and fear-conditioning paradigms. Animals receiving sevoflurane alone showed impaired spatial recognition and fear memory relative to controls. Co-administration of hydrogen gas significantly restored cognitive function compared with sevoflurane exposure alone. At the molecular level, hydrogen gas inhibited NF-κB phosphorylation and its translocation into the nucleus, while also reducing the levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α. These findings indicate that NF-κB pathway inhibition and attenuation of proinflammatory cytokine release are key mechanisms by which hydrogen gas counters sevoflurane-associated neurotoxicity in the neonatal rat brain.

Mechanism

Hydrogen gas inhibits NF-κB phosphorylation and nuclear translocation, thereby reducing the release of IL-1β, IL-6, and TNF-α, which collectively attenuates sevoflurane-induced neurotoxicity in the developing rat brain.