期刊
JOURNAL OF NEUROINFLAMMATION
卷 15, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12974-018-1256-8
关键词
C1q/TNF-related protein 9; Adiponectin receptor 1; Intracerebral hemorrhage; Neuroinflammation; Adenosine monophosphate-activated protein kinase
资金
- National Institutes of Health [NS091042, NS082184]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P01NS082184, R01NS091042] Funding Source: NIH RePORTER
Background: Neuroinflammation is a crucial factor contributing to neurological injuries after intracerebral hemorrhage (ICH). C1WINF-related protein 9 (CTRP9), an agonist of adiponectin receptor 1 (AdipoR1), has recently been shown to reduce inflammatory responses in systemic diseases. The objective of this study was to investigate the protective role of CTRP9 against neuroinflammation after ICH in a mouse model and to explore the contribution of adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor kappa B (NF kappa B) pathway in AdipoR1-mediated protection. Methods: Adult male CD1 mice (n = 218) were randomly assigned to different groups for the study. ICH was induced via intrastriatal injection of bacterial collagenase. Recombinant CTRP9 (rCTRP9) was administered intranasally at 1 h after ICH. To elucidate the underlying mechanism, AdipoR1 small interfering ribonucleic acid (siRNA) and selective phosphorylated AMPK inhibitor Dorsomorphin were administered prior to rCTRP9 treatment. Brain edema, short- and long-term neurobehavior evaluation, blood glucose level, western blot, and immunofluorescence staining were performed. Results: Endogenous CTRP9 and AdipoR1 expression was increased and peaked at 24 h after ICH. AdipoRl was expressed by microglia, neurons, and astrocytes. Administration of rCTRP9 reduced brain edema, improved short- and long-term neurological function, enhanced the expression of AdipoRl and p-AMPK, and decreased the expression of phosphorylated NF kappa B and inflammatory cytokines after ICH. The protective effects of rCTRP9 were abolished by administration of AdipoR1 siRNA and Dorsomorphin. Conclusions: Our findings demonstrated that administration of rCTRP9 attenuated neuroinflammation through AdipoR1/AMPK/NF kappa B signaling pathway after ICH in mice, thereby reducing brain edema and improving neurological function after experimental ICH in mice. Therefore, CTRP9 may provide a potential therapeutic strategy to alleviate neuroinflammation in ICH patients.
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