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Article: Activation of adenosine A3 receptor reduces early brain injury by alleviating neuroinflammation after subarachnoid hemorrhage in elderly rats

TitleActivation of adenosine A3 receptor reduces early brain injury by alleviating neuroinflammation after subarachnoid hemorrhage in elderly rats
Authors
Keywordssubarachnoid hemorrhage
microglial polarization
adenosine A3 receptor
anti-inflammation
Issue Date2020
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactaging.com
Citation
Aging, 2020, v. 13 n. 1, p. 694-713 How to Cite?
AbstractThe incidence of subarachnoid hemorrhage (SAH) and hazard ratio of death increase with age. Overactivation of microglia contributes to brain damage. This study aimed to investigate the effects of A3 adenosine receptors (A3R) activation on neurofunction and microglial phenotype polarization in the context of SAH in aged rats. The A3R agonist (CI-IB-MECA) and antagonist (MRS1523) were used in the SAH model. Microglia were cultured to mimic SAH in the presence or absence of CI-IB-MECA and/or siRNA for A3R. The neurofunction and status of the microglial phenotype were evaluated. The P38 inhibitor SB202190 and the STAT6 inhibitor AS1517499 were used to explore the signaling pathway. The results showed that SAH induced microglia to polarize to the M(LPS) phenotype both in vivo and in vitro. CI-IB-MECA distinctly skewed microglia towards the M(IL-4) phenotype and ameliorated neurological dysfunction, along with the downregulation of inflammatory cytokines. Knockdown of A3R or inhibition of P38 and/or STAT6 weakened the effects of CI-IB-MECA on microglial phenotypic shifting. Collectively, our findings suggest that activation of A3R exerted anti-inflammatory and neuroprotective effects by regulating microglial phenotype polarization through P38/STAT6 pathway and indicated that A3R agonists may be a promising therapeutic options for the treatment of brain injury after SAH.
Persistent Identifierhttp://hdl.handle.net/10722/294703
ISSN
2020 Impact Factor: 5.682
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorLi, P-
dc.contributor.authorLi, X-
dc.contributor.authorDeng, P-
dc.contributor.authorWang, D-
dc.contributor.authorBai, X-
dc.contributor.authorLi, Y-
dc.contributor.authorLuo, C-
dc.contributor.authorBelguise, K-
dc.contributor.authorWang, X-
dc.contributor.authorWei, X-
dc.contributor.authorXia, Z-
dc.contributor.authorYi, B-
dc.date.accessioned2020-12-08T07:40:40Z-
dc.date.available2020-12-08T07:40:40Z-
dc.date.issued2020-
dc.identifier.citationAging, 2020, v. 13 n. 1, p. 694-713-
dc.identifier.issn1945-4589-
dc.identifier.urihttp://hdl.handle.net/10722/294703-
dc.description.abstractThe incidence of subarachnoid hemorrhage (SAH) and hazard ratio of death increase with age. Overactivation of microglia contributes to brain damage. This study aimed to investigate the effects of A3 adenosine receptors (A3R) activation on neurofunction and microglial phenotype polarization in the context of SAH in aged rats. The A3R agonist (CI-IB-MECA) and antagonist (MRS1523) were used in the SAH model. Microglia were cultured to mimic SAH in the presence or absence of CI-IB-MECA and/or siRNA for A3R. The neurofunction and status of the microglial phenotype were evaluated. The P38 inhibitor SB202190 and the STAT6 inhibitor AS1517499 were used to explore the signaling pathway. The results showed that SAH induced microglia to polarize to the M(LPS) phenotype both in vivo and in vitro. CI-IB-MECA distinctly skewed microglia towards the M(IL-4) phenotype and ameliorated neurological dysfunction, along with the downregulation of inflammatory cytokines. Knockdown of A3R or inhibition of P38 and/or STAT6 weakened the effects of CI-IB-MECA on microglial phenotypic shifting. Collectively, our findings suggest that activation of A3R exerted anti-inflammatory and neuroprotective effects by regulating microglial phenotype polarization through P38/STAT6 pathway and indicated that A3R agonists may be a promising therapeutic options for the treatment of brain injury after SAH.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactaging.com-
dc.relation.ispartofAging-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectsubarachnoid hemorrhage-
dc.subjectmicroglial polarization-
dc.subjectadenosine A3 receptor-
dc.subjectanti-inflammation-
dc.titleActivation of adenosine A3 receptor reduces early brain injury by alleviating neuroinflammation after subarachnoid hemorrhage in elderly rats-
dc.typeArticle-
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hk-
dc.identifier.authorityXia, Z=rp00532-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.18632/aging.202178-
dc.identifier.pmid33253120-
dc.identifier.pmcidPMC7835045-
dc.identifier.scopuseid_2-s2.0-85099537379-
dc.identifier.hkuros320577-
dc.identifier.volume13-
dc.identifier.issue1-
dc.identifier.spage694-
dc.identifier.epage713-
dc.publisher.placeUnited States-

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