Arterial Baroreflex Dysfunction Promotes Neuroinflammation by Activating the Platelet CD40LNuclear Factor Kappa B Signaling Pathway in Microglia and Astrocytes
作者单位：Institute of Pharmacology2School of Chemistry and Pharmaceutical EngineeringShandong First Medical University & Shandong Academy of Medical Science
会议名称：《2023年全国心血管药理学学术会议》
会议日期：1000年
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：supported by grants from the National Natural Science Foundation of China (81173061) the Natural Science Foundation of Shandong Province of China (ZR2017MH048,ZR202111120207) the Academic Promotion Programme of Shandong First Medical University (2019LJ003) the Collaborative Innovation Center for Research and Development of Traditional Chinese Medicine in Mount Tai (zd099)
关 键 词：Arterial baroreflex Neuroinflammation Astrocytes Microglia Platelet CD40L
摘 要：Arterial baroreflex(ABR) dysfunction has previously been associated with neuroinflammation,the most common pathological feature of neurological ***,the mechanisms mediating ABR dysfunction-induced neuroinflammation are not fully *** the present study,we investigated the role of platelet CD40 ligand(CD40L) in neuroinflammation in an in vivo model of ABR dysfunction,and microglia and astrocyte activation in *** dysfunction was induced in Sprague-Dawley rats by sinoaortic denervation(SAD).We used ELSA and immunofluorescence to assess the effect of platelet CD40L on glial cell polarization and the secretion of inflammatory *** flow cytometry,we found that rats subjected to SAD showed a high level of platelet microaggregation and upregulation of CD40L on the platelet *** promotion of platelet invasion and accumulation was also observed in the brain tissues of rats subjected to *** the animal model and cultured N9 microglia/C6 astrocytoma cells,platelet CD40L overexpression promoted neuroinflammation and activated M1 microglia,A1 astrocytes,and the nuclear factor kappa B(NFκB) signaling *** effects were partially blocked by inhibiting platelet activity with clopidogrel or inhibiting CD40L-mediated *** results suggest that during ABR dysfunction,CD40L signaling in platelets converts microglia to the M1 phenotype and astrocytes to the A1 phenotype,activating NFκB and resulting in ***,our study provides a novel understanding of the pathogenesis of ABR dysfunction-induced neuroinflammation and indicates that targeting platelet CD40L is beneficial for treating central nervous system(CNS) disorders associated with ABR dysfunction.
