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

Ji Che1, Yuanyuan Wu1, Jing Dong1

  • 1Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China.

Experimental Neurology
|December 5, 2024
PubMed
Abstract

Insights

Histamine receptor 3 (H3) antagonist thioperamide protects the developing brain from anesthesia-induced (sevoflurane) myelination damage and neurobehavioral deficits. H3 receptor blockade offers a potential therapeutic strategy.

Area of Science:

  • Neuroscience
  • Anesthesiology
  • Developmental Biology

Background:

  • Inhalational anesthetics like sevoflurane can harm the developing brain's myelination.
  • This study investigates thioperamide, a histamine receptor 3 (H3) antagonist, for its protective effects.

Purpose of the Study:

  • To evaluate thioperamide's efficacy in preventing sevoflurane-induced hypomyelination and neurobehavioral deficits.
  • To elucidate the underlying mechanisms of thioperamide's neuroprotective action.

Main Methods:

  • Neonatal mice received sevoflurane exposure and thioperamide treatment.
  • Assessed myelination in the hippocampus and corpus callosum, alongside neurobehavioral tests.
  • Conducted in vitro experiments on primary oligodendrocyte progenitor cells (OPCs).

Main Results:

  • Thioperamide significantly mitigated sevoflurane-induced myelination and neurobehavioral impairments.
  • In vitro, thioperamide reversed sevoflurane's negative effects on OPC migration, proliferation, and differentiation.
  • The protective mechanism involves the H3 receptor-mediated GSK-3β/β-catenin pathway.

Conclusions:

  • H3 receptor antagonism with thioperamide protects the developing brain from sevoflurane-induced neurotoxicity.
  • H3 receptor is a promising therapeutic target for preventing anesthetic-induced developmental neurotoxicity.
Keywords:
Developing brainHistamine receptor 3MyelinationOligodendrocyte progenitor cellsSevoflurane

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