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.author | Ocak, Umut | |
dc.contributor.author | Huang, Lei | |
dc.contributor.author | Zuo, Gang | |
dc.contributor.author | Yan, Jun | |
dc.contributor.author | Hu, Xin | |
dc.contributor.author | Song, Zhijun | |
dc.contributor.author | Zhang, John H. | |
dc.contributor.buuauthor | Ocak, Pınar Eser | |
dc.contributor.department | Bursa Uludağ Üniversitesi/Tıp Fakültesi/Nöroşirürji Anabilim Dalı. | tr_TR |
dc.contributor.orcid | 0000-0003-0132-9927 | tr_TR |
dc.contributor.scopusid | 57200969645 | tr_TR |
dc.date.accessioned | 2023-01-30T07:03:06Z | |
dc.date.available | 2023-01-30T07:03:06Z | |
dc.date.issued | 2020-01-14 | |
dc.description.abstract | Objective: 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.sponsorship | National Institute of Neurological Disorders and Stroke (P01NS082184) | en_US |
dc.description.sponsorship | Loma Linda University Neurosurgery Department Research Fund (8180029) | en_US |
dc.description.sponsorship | United States Department of Health & Human Services National Institutes of Health (NIH) - USA (P01NS082184) | en_US |
dc.identifier.citation | Ocak, 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.endpage | 547 | tr_TR |
dc.identifier.issn | 1073-2322 | |
dc.identifier.issn | 1540-0514 | |
dc.identifier.issue | 4 | tr_TR |
dc.identifier.pubmed | 32028357 | tr_TR |
dc.identifier.scopus | 2-s2.0-85084393287 | tr_TR |
dc.identifier.startpage | 539 | tr_TR |
dc.identifier.uri | https://doi.org/10.1097/SHK.0000000000001516 | |
dc.identifier.uri | https://journals.lww.com/shockjournal/Fulltext/2020/10000/Inhibition_of_PAR_2_Attenuates_Neuroinflammation.14.aspx | |
dc.identifier.uri | http://hdl.handle.net/11452/30704 | |
dc.identifier.volume | 54 | tr_TR |
dc.identifier.wos | 000619500300014 | tr_TR |
dc.indexed.pubmed | PubMed | en_US |
dc.indexed.scopus | Scopus | en_US |
dc.indexed.wos | SCIE | en_US |
dc.language.iso | en | en_US |
dc.publisher | Lippincott Williams & Wilkins | en_US |
dc.relation.collaboration | Yurt dışı | tr_TR |
dc.relation.collaboration | Sanayi | tr_TR |
dc.relation.journal | Shock | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi | tr_TR |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | General & internal medicine | en_US |
dc.subject | Hematology | en_US |
dc.subject | Surgery | en_US |
dc.subject | Cardiovascular system & cardiology | en_US |
dc.subject | Cardiac arrest | en_US |
dc.subject | Global cerebral ischemia | en_US |
dc.subject | Neurocognitive | en_US |
dc.subject | Neuroinflammation | en_US |
dc.subject | Protease activated receptor 2 | en_US |
dc.subject | Protease-activated receptors | en_US |
dc.subject | Intestinal ischemia-reperfusion | en_US |
dc.subject | Subarachnoid hemorrhage | en_US |
dc.subject | Cognitive dysfunction | en_US |
dc.subject | Global-ischemia | en_US |
dc.subject | Brain | en_US |
dc.subject | Trpytase | en_US |
dc.subject | Injury | en_US |
dc.subject | Pathway | en_US |
dc.subject | Cells | en_US |
dc.subject.emtree | Proteinase activated receptor 2 | en_US |
dc.subject.emtree | Animal | en_US |
dc.subject.emtree | Asphyxia | en_US |
dc.subject.emtree | Genetics | en_US |
dc.subject.emtree | Heart arrest | en_US |
dc.subject.emtree | Male | en_US |
dc.subject.emtree | MAPK signaling | en_US |
dc.subject.emtree | Metabolism | en_US |
dc.subject.emtree | Pathophysiology | en_US |
dc.subject.emtree | Physiology | en_US |
dc.subject.emtree | Rat | en_US |
dc.subject.emtree | Sprague dawley rat | en_US |
dc.subject.emtree | Western blotting | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Asphyxia | en_US |
dc.subject.mesh | Blotting, western | en_US |
dc.subject.mesh | Heart arrest | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | MAP kinase signaling system | en_US |
dc.subject.mesh | Rats | en_US |
dc.subject.mesh | Rats, sprague-dawley | en_US |
dc.subject.mesh | Receptor, PAR-2 | en_US |
dc.subject.scopus | Minocycline; Microglia; Anti-Bacterial Agents | en_US |
dc.subject.wos | Critical care medicine | en_US |
dc.subject.wos | Hematology | en_US |
dc.subject.wos | Surgery | en_US |
dc.subject.wos | Peripheral vascular disease | en_US |
dc.title | Inhibition of PAR-2 attenuates neuroinflammation and improves short-term neurocognitive functions via ERK1/2 signaling following asphyxia-induced cardiac arrest in rats | en_US |
dc.type | Article | |
dc.wos.quartile | Q2 | en_US |