Myelination Trajectory and Microglial Dynamics Following Repeated Sevoflurane Exposure in Developing Brain.
Summary
In neonatal mice, repeated sevoflurane exposure impaired fine motor and cognitive functions and disrupted myelination in hippocampus and corpus callosum via microglial activation and lipid droplet accumulation. Conditioned media from sevoflurane-treated microglia suppressed OPC proliferation/differentiation, while minocycline or CSF1R inhibitor PLX5622 mitigated neuroinflammation and hypomyelination.
Key Findings
- Repeated sevoflurane exposure impaired fine motor and cognitive functions in neonatal mice.
- Myelination markers (MBP, PDGFR-α) were dysregulated in hippocampus and corpus callosum, with microglial lipid droplet accumulation.
- Conditioned media from sevoflurane-treated microglia inhibited OPC proliferation/differentiation.
- Microglial inhibition/depletion (minocycline, PLX5622) alleviated neuroinflammation and hypomyelination.
Clinical Implications
While not immediately practice-changing, the data caution against repeated or prolonged sevoflurane exposure in neonates/infants and suggest microglia-focused interventions as potential neuroprotective strategies to be tested clinically.
Why It Matters
This mechanistic study advances understanding of anesthetic neurotoxicity by identifying microglial hyperactivation as a key driver of hypomyelination after sevoflurane, and demonstrates pharmacologic rescue. It provides targets and pathways for preventive strategies in vulnerable developing brains.
Limitations
- Animal model limits direct clinical translatability of dose/timing to human infants.
- Long-term functional outcomes and sex-specific effects were not detailed.
Future Directions
Define exposure thresholds and windows of vulnerability, test microglia-targeted neuroprotection in large animal models, and evaluate neurodevelopmental outcomes in prospective pediatric cohorts.
Study Information
- Study Type
- Basic/Mechanistic
- Research Domain
- Pathophysiology
- Evidence Level
- V - Preclinical mechanistic animal and cell culture study elucidating pathways.
- Study Design
- OTHER