title: Blocking Sympathetic Nervous System Reverses Partially Stroke-Induced Immunosuppression but does not Aggravate Functional Outcome After Experimental Stroke in Rats.
abstract: Stoke results in activation of the sympathetic nervous system (SNS), inducing systemic immunosuppression. However, the potential mechanisms underlying stroke-induced immunosuppression remain unclear. Here, we determined the SNS effects on functional outcome and explored the interactions among SNS, β-arrestin2 and nuclear factor-κB (NF-κB) after experimental stroke in rats. In the current study, stroke was induced by a transient middle cerebral artery occlusion (MCAO) in rats, and SNS activity was inhibited by intraperitoneal injection of 6-hydroxydopamine HBr (6-OHDA). 7.0 T Micro-MRI and Longa score were employed to assess the functional outcome after stroke. Flow cytometry and ELISA assay were used to measure the expression of MHC class II, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Western blot was conducted to analyze β-arrestin2 and NF-κB protein expression levels after experimental stroke. We found significantly increased infarct volumes and functional impairment after MCAO at different post-surgery time points, which were not aggravated by 6-OHDA treatment. SNS blockade partially reversed the expression of MHC class II after stroke over time, as well as TNF-α and IFN-γ levels in lipopolysaccharide-stimulated macrophages in vitro. Treatment of MCAO rats with SNS-inhibitor significantly diminished NF-κB activation and enhanced β-arrestin2 expression after stroke. This study suggests that pharmacological SNS inhibition dose not aggravate functional outcome after stroke. Stroke-induced immunosuppression may be involved in the SNS-β-arrestin2-NF-κB pathway.
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, 87, Dingjiaqiao Road, Nanjing, 210009, China.
authors.forename: Qi-Wen
authors.initials: QW
authors.lastname: Deng
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, 87, Dingjiaqiao Road, Nanjing, 210009, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, 87, Dingjiaqiao Road, Nanjing, 210009, China. yanfuling218@163.com.
authors.forename: Fu-Ling
authors.initials: FL
authors.lastname: Yan
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, 87, Dingjiaqiao Road, Nanjing, 210009, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, 87, Dingjiaqiao Road, Nanjing, 210009, China.
authors.forename: Fang-Lan
authors.initials: FL
authors.lastname: Xing
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, 87, Dingjiaqiao Road, Nanjing, 210009, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zuo
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, 87, Dingjiaqiao Road, Nanjing, 210009, China.
authors.forename: Han-Qing
authors.initials: HQ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D007165:Immunosuppression Therapy / Q000379:methods*; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020521:Stroke / Q000276:immunology* / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D016627:Oxidopamine
keywords: Immunosuppression; Nuclear factor-κB; Stroke; Sympathetic nervous system; β-Arrestin2