Therapeutic effect of dexmedetomidine on intracerebral hemorrhage via regulating NLRP3.

Apr 10, 2019European review for medical and pharmacological sciences

Dexmedetomidine's therapeutic effects on brain bleeding by controlling inflammation

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Dexmedetomidine treatment significantly decreased intracerebral hemorrhage (ICH) volume and cerebral edema in mice.

Clinical symptoms in ICH mice improved with dexmedetomidine administration.
Levels of inflammatory markers NLRP3, ASC, Caspase-1, and IL-1β were reduced in treated mice compared to controls.
Treatment resulted in decreased levels of CD11b+CD45int and IL-6, while TGF-β content increased.
Evans Blue leakage, indicating blood-brain barrier (BBB) permeability, was reduced in the treatment group.
Protein and mRNA levels of Claudin-5 and ZO-1, which are important for BBB integrity, were upregulated with treatment.

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OBJECTIVE: To investigate the protective effect of dexmedetomidine on intracerebral hemorrhage (ICH) mice and the underlying mechanism.

MATERIALS AND METHODS: The in vivo ICH model was induced by the injection of autologous blood in C57BL/6 mice. Mice were randomly assigned into control group (no specific treatment) and treatment group (dexmedetomidine administration). Mouse neuronal deficits were evaluated by modified neurological severity scores (mNSS) and Corner Turn Test. ICH volume and cerebral edema at the hemisphere of lesions were determined. Inflammatory response at post-ICH was examined by flow cytometry and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The integrity and permeability of blood brain barrier (BBB) were detected by Western blot and Evans Blue extravasation.

RESULTS: Dexmedetomidine treatment markedly alleviated the clinical symptoms of ICH mice, and decreased ICH volume and cerebral edema. QRT-PCR data revealed down-regulated levels of NLRP3, ASC, Caspase-1, and IL-1β in mice of the treatment group relative to controls. Moreover, dexmedetomidine administration decreased contents of CD11b+CD45int, IL-6, and IL-1β, but elevated TGF-β content in treatment group. The Evans Blue leakage was reduced in mice of the treatment group. Both protein and mRNA levels of Claudin-5 and ZO-1 were upregulated in the treatment group.

CONCLUSIONS: Dexmedetomidine remarkably inhibits the activation of inflammasome, alleviates secondary cerebral injury and inflammation, and protects the integrity and permeability of BBB at post-ICH.

Therapeutic effect of dexmedetomidine on intracerebral hemorrhage via regulating NLRP3.

Abstract

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