2. Academic Validation
  3. Inhibition of histamine receptor 3 alleviates sevoflurane-induced hypomyelination and neurobehavioral deficits

Inhibition of histamine receptor 3 alleviates sevoflurane-induced hypomyelination and neurobehavioral deficits

  • Exp Neurol. 2025 Mar:385:115086. doi: 10.1016/j.expneurol.2024.115086.
Ji Che 1,  Yuanyuan Wu 2,  Jing Dong 3,  Xuliang Jiang 3,  Li Yang 3,  Yali Chen 3,  Jun Zhang 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China. Electronic address: 21111230054@m.fudan.edu.cn.
  • 2 Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China. Electronic address: 22111230064@m.fudan.edu.cn.
  • 3 Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China.
  • 4 Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China. Electronic address: zhangjun_@fudan.edu.cn.
PMID: 39637962 DOI: 10.1016/j.expneurol.2024.115086
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords

Developing brain; Histamine receptor 3; Myelination; Oligodendrocyte progenitor cells; Sevoflurane.

Figures
Products
Inhibitors & Agonists
Other Products