Blocking Sympathetic Nervous System Reverses Partially Stroke-Induced Immunosuppression but does not Aggravate Functional Outcome After Experimental Stroke in Rats.
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.
['Deng|Qi-Wen|QW|', 'Yang|Heng|H|', 'Yan|Fu-Ling|FL|', 'Wang|Huan|H|', 'Xing|Fang-Lan|FL|', 'Zuo|Lei|L|', 'Zhang|Han-Qing|HQ|']
D000818:Animals D007165:Immunosuppression Therapy D008297:Male D016627:Oxidopamine D051381:Rats D017207:Rats, Sprague-Dawley D020127:Recovery of Function D015398:Signal Transduction D020521:Stroke D013564:Sympathetic Nervous System D016896:Treatment Outcome
Sympathetic nervous system Immunosuppression Stroke β-Arrestin2 Nuclear factor-κB