Inhibition of histamine receptor 3 alleviates sevoflurane-induced hypomyelination and neurobehavioral deficits
Inhalational anesthetic sevoflurane can cause myelination damage in developing brain. This study examines the effects of histamine receptor 3 (H3) antagonist thioperamide on sevoflurane-induced hypomyelination and neurobehavioral deficits. Neonatal C57BL/6 mice were exposed to sevoflurane for consec...
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Veröffentlicht in: | Experimental neurology 2025-03, Vol.385, p.115086, Article 115086 |
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Zusammenfassung: | Inhalational anesthetic sevoflurane can cause myelination damage in developing brain. This study examines the effects of histamine receptor 3 (H3) antagonist thioperamide on sevoflurane-induced hypomyelination and neurobehavioral deficits.
Neonatal C57BL/6 mice were exposed to sevoflurane for consecutive three days and treated with H3 receptor antagonist thioperamide. Myelination was assessed in the hippocampus and corpus callosum. The neurobehavioral functions were also examined. Primary oligodendrocyte progenitor cells (OPCs) were used for in vitro experiments and the underlying mechanism.
Inhibition of H3 receptor with thioperamide significantly alleviated sevoflurane-induced impairments in myelination and neurobehavioral functions. In vitro experiments showed that thioperamide reversed the effects of sevoflurane on OPCs migration, proliferation and differentiation into mature oligodendrocytes. Mechanistically, thioperamide improved sevoflurane-induced hypomyelination may through H3 receptor-mediated GSK-3β/β-catenin pathway.
H3 receptor antogonist thioperamide could protect developing brain against hypomyelination and neurobehavioral deficits after repeated sevoflurane exposure. Therefore H3 receptor is a potential target for preventing anesthetic-induced developmental neurotoxicity.
•H3 receptor inhibition significantly mitigates sevoflurane-induced hypomyelination in developing brain.•H3 receptor antagonist thioperamide improves neurobehavioral functions at adolescence when neonatal sevoflurane exposure.•GSK-3β/β-catenin signaling mediates the beneficial effects of thioperamide on myelination via H3 receptor.•Thioperamide alleviates rather than worsens sevoflurane-induced blood-brain barrier disruption. |
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ISSN: | 0014-4886 1090-2430 1090-2430 |
DOI: | 10.1016/j.expneurol.2024.115086 |