Inhibition of PAR-2 attenuates neuroinflammation and improves short-term neurocognitive functions via ERK1/2 signaling following asphyxia-induced cardiac arrest in rats

dc.contributor.authorOcak, Umut
dc.contributor.authorHuang, Lei
dc.contributor.authorZuo, Gang
dc.contributor.authorYan, Jun
dc.contributor.authorHu, Xin
dc.contributor.authorSong, Zhijun
dc.contributor.authorZhang, John H.
dc.contributor.buuauthorOcak, Pınar Eser
dc.contributor.departmentBursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroşirürji Anabilim Dalı.tr_TR
dc.contributor.orcid0000-0003-0132-9927tr_TR
dc.contributor.scopusid57200969645tr_TR
dc.date.accessioned2023-01-30T07:03:06Z
dc.date.available2023-01-30T07:03:06Z
dc.date.issued2020-01-14
dc.description.abstractObjective: Global cerebral ischemia-induced neuroinflammation causes neurofunctional impairment following cardiac arrest. Previous studies have demonstrated that the activation of protease-activated receptor-2 (PAR-2) contributes to neuroinflammation. In the present study, we aimed to determine the potential treatment effect of PAR-2 inhibition against neuroinflammation in the setting of asphyxial CA(ACA) in rats. Methods: A total of 116 adult, male Sprague-Dawley rats were randomly divided into Sham (n = 18) and ACA (n = 98) groups. Time course, short-term outcome, and mechanism studies were conducted. All drugs were delivered intranasally. The effect of PAR-2 inhibitor FSLLRY-NH2 on neurocognitive functions was assessed by neurologic deficit score, number of seizures, and T-maze test, while hippocampal neuronal degeneration was evaluated by Fluoro-Jade C staining after ACA. Western blotting was performed for the mechanism study at 24 h following ACA. Selective PAR-2 agonist (AC55541) and ERK1/2 inhibitor (PD98059) were used for intervention. Results: Inhibition of PAR-2 decreased neuroinflammation, reduced the number of degenerating hippocampal neurons and improved neurocognitive functions following ACA. PAR-2 activator alone exerted opposite effects to PAR-2 inhibitor. PAR-2mediated the augmented brain levels of proinflammatory cytokines by promoting the phosphorylation of ERK1/2. Conclusions: PAR-2 inhibition diminished neuroinflammation and thereby reduced hippocampal neuronal degeneration and neurocognitive impairment following ACA. This effect was at least partly mediated via the PAR-2/ERK1/2 signaling.en_US
dc.description.sponsorshipNational Institute of Neurological Disorders and Stroke (P01NS082184)en_US
dc.description.sponsorshipLoma Linda University Neurosurgery Department Research Fund (8180029)en_US
dc.description.sponsorshipUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA (P01NS082184)en_US
dc.identifier.citationOcak, U. vd. (2020). "Inhibition of PAR-2 attenuates neuroinflammation and improves short-term neurocognitive functions via ERK1/2 signaling following asphyxia-induced cardiac arrest in rats". Shock, 54(4), 539-547.en_US
dc.identifier.endpage547tr_TR
dc.identifier.issn1073-2322
dc.identifier.issn1540-0514
dc.identifier.issue4tr_TR
dc.identifier.pubmed32028357tr_TR
dc.identifier.scopus2-s2.0-85084393287tr_TR
dc.identifier.startpage539tr_TR
dc.identifier.urihttps://doi.org/10.1097/SHK.0000000000001516
dc.identifier.urihttps://journals.lww.com/shockjournal/Fulltext/2020/10000/Inhibition_of_PAR_2_Attenuates_Neuroinflammation.14.aspx
dc.identifier.urihttp://hdl.handle.net/11452/30704
dc.identifier.volume54tr_TR
dc.identifier.wos000619500300014tr_TR
dc.indexed.pubmedPubMeden_US
dc.indexed.scopusScopusen_US
dc.indexed.wosSCIEen_US
dc.language.isoenen_US
dc.publisherLippincott Williams & Wilkinsen_US
dc.relation.collaborationYurt dışıtr_TR
dc.relation.collaborationSanayitr_TR
dc.relation.journalShocken_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergitr_TR
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectGeneral & internal medicineen_US
dc.subjectHematologyen_US
dc.subjectSurgeryen_US
dc.subjectCardiovascular system & cardiologyen_US
dc.subjectCardiac arresten_US
dc.subjectGlobal cerebral ischemiaen_US
dc.subjectNeurocognitiveen_US
dc.subjectNeuroinflammationen_US
dc.subjectProtease activated receptor 2en_US
dc.subjectProtease-activated receptorsen_US
dc.subjectIntestinal ischemia-reperfusionen_US
dc.subjectSubarachnoid hemorrhageen_US
dc.subjectCognitive dysfunctionen_US
dc.subjectGlobal-ischemiaen_US
dc.subjectBrainen_US
dc.subjectTrpytaseen_US
dc.subjectInjuryen_US
dc.subjectPathwayen_US
dc.subjectCellsen_US
dc.subject.emtreeProteinase activated receptor 2en_US
dc.subject.emtreeAnimalen_US
dc.subject.emtreeAsphyxiaen_US
dc.subject.emtreeGeneticsen_US
dc.subject.emtreeHeart arresten_US
dc.subject.emtreeMaleen_US
dc.subject.emtreeMAPK signalingen_US
dc.subject.emtreeMetabolismen_US
dc.subject.emtreePathophysiologyen_US
dc.subject.emtreePhysiologyen_US
dc.subject.emtreeRaten_US
dc.subject.emtreeSprague dawley raten_US
dc.subject.emtreeWestern blottingen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAsphyxiaen_US
dc.subject.meshBlotting, westernen_US
dc.subject.meshHeart arresten_US
dc.subject.meshMaleen_US
dc.subject.meshMAP kinase signaling systemen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, sprague-dawleyen_US
dc.subject.meshReceptor, PAR-2en_US
dc.subject.scopusMinocycline; Microglia; Anti-Bacterial Agentsen_US
dc.subject.wosCritical care medicineen_US
dc.subject.wosHematologyen_US
dc.subject.wosSurgeryen_US
dc.subject.wosPeripheral vascular diseaseen_US
dc.titleInhibition of PAR-2 attenuates neuroinflammation and improves short-term neurocognitive functions via ERK1/2 signaling following asphyxia-induced cardiac arrest in ratsen_US
dc.typeArticle
dc.wos.quartileQ2en_US

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