Astrocyte morphological remodeling regulates consciousness state transitions induced by inhaled general anesthesia.

Summary

Inhaled anesthetics dynamically remodel astrocyte fine processes via Ezrin phosphorylation, weakening astrocyte–synapse interactions and increasing sevoflurane sensitivity. Disrupting astrocytic Ezrin phosphorylation enhances tonic GABAergic inhibition and decreases pyramidal neuron excitability, implicating astrocyte morphology as an active regulator of anesthesia-induced consciousness transitions.

Key Findings

• Inhaled general anesthetics induce reversible impairments in astrocyte fine processes via Ezrin phosphorylation in somatosensory cortex.
• Genetic deletion or phosphorylation disruption of Ezrin reduces astrocyte–synapse interactions and increases in vivo sensitivity to sevoflurane.
• Disrupting astrocytic Ezrin phosphorylation enhances tonic GABA inhibition and lowers pyramidal neuron excitability during anesthesia.

Clinical Implications

While preclinical, the findings suggest potential biomarkers (e.g., astrocytic Ezrin signaling) and targets to fine-tune anesthetic depth or hasten emergence. They also caution that glial modulators or conditions affecting astrocytic morphology could alter anesthetic requirements.

Limitations

• Preclinical animal study with cortical focus; human validation is lacking
• Findings centered on sevoflurane and somatosensory cortex; generalizability across anesthetics and brain regions requires testing

Future Directions

Validate astrocytic Ezrin signaling changes in humans (e.g., CSF/exosomal markers), test causality across anesthetic classes and brain regions, and explore glia-targeted modulators to control anesthetic depth and emergence.