Sodium Butyrate reverses sevoflurane-induced myelination impairment and neurobehavioral deficits in neonatal mice

Early-life exposure to sevoflurane, a common anesthetic, is a significant risk factor for abnormal neurodevelopment, often leading to impaired myelination and neurobehavioral deficits. Current strategies to mitigate these long-term neurological sequelae are limited. Sodium butyrate (NaB), a short-chain fatty acid, is known for its epigenetic regulatory activity and neuroprotective effects in various neurological disorders. However, its specific role in counteracting sevoflurane-induced myelination impairment and the underlying molecular mechanisms remained unclear, representing a critical gap this study addresses.

Researchers established an in vivo neonatal mouse model of sevoflurane exposure to investigate its effects on myelination and neurobehavioral function. An intervention with Sodium Butyrate was administered to evaluate its potential to ameliorate these sevoflurane-induced impairments. Additionally, in vitro experiments utilized human oligodendrocyte precursor cells (HOPCs) directly treated with different concentrations of NaB to examine its effects on cell proliferation, migration, differentiation, and related molecular signaling pathways, including H3K9ac, BDNF, and TrkB phosphorylation.

Repeated sevoflurane exposure during the critical period of brain development in neonatal mice significantly inhibited the proliferation and differentiation of oligodendrocyte precursor cells (OPCs), leading to impaired myelination and subsequent neurobehavioral deficits. NaB intervention effectively ameliorated these sevoflurane-induced myelination impairments and neurobehavioral dysfunction. Mechanistically, NaB achieved these protective effects by regulating histone H3 lysine 9 acetylation (H3K9ac). This epigenetic modulation led to the upregulation of brain-derived neurotrophic factor (BDNF) expression and promoted tropomyosin receptor kinase B (TrkB) phosphorylation, consequently increasing phosphorylated TrkB (p-TrkB) levels. These findings highlight a specific pathway through which NaB exerts its neuroprotective actions.

NaB intervention significantly ameliorated sevoflurane-induced myelination impairment and neurobehavioral dysfunction by regulating H3K9ac and increasing BDNF and p-TrkB levels.