A perfect storm: consequences of excess inhibitory neurotransmission after anaesthesia and surgery.

Orser, Beverley A; Brenna, Connor T A; Hemmings, Hugh C; Wang, Dian-Shi · Br J Anaesth · 2026

Where this comes from

Abstract

Perioperative neurocognitive disorders may arise from three complementary mechanisms that, together, cause excessive inhibitory neurotransmission. Sustained accumulation of type A γ-aminobutyric acid (GABA<sub>A</sub>) receptors on the surface of neurones, aberrant release of GABA from astrocytes, and increased production of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) can all enhance the amplitude of tonic inhibitory conductance, and in concert could disrupt network synchrony and impair cognition after anaesthesia and surgery. The report by Wan and colleagues identifies a key pathway by which sevoflurane activates calcium (Ca<sup>2+</sup>)/calmodulin-dependent protein kinase II (CaMKII), which impairs GABA<sub>A</sub> receptor internalisation and thereby promotes receptor accumulation on the neuronal surface. The accumulation of GABA<sub>A</sub> receptors is expected to interact synergistically with increased concentrations of GABA and H<sub>2</sub>O<sub>2</sub> to drive excess inhibitory neurotransmission. Targeting even one of these three factors might be sufficient to preserve cognition after anaesthesia and surgery.

Medical subject headings