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Background: In Parkinson's disease (PD), inflammation may lead to the degeneration of dopaminergic (DAergic) neurons. Previous studies showed that inflammatory mediators mainly contributed to this phenomenon. On the other hand, invasive neuromodulation methods such as deep brain stimulation (DBS) have better therapeutic effects for PD. One possibility is that DBS improves PD by influencing inflammation. Therefore, we further explored the mechanisms underlying inflammatory mediators and DBS in the pathogenesis of PD. Methods: We measured serum levels of two inflammatory markers, namely RANTES (regulated on activation, normal T cell expressed and secreted) and tumor necrosis factor‐alpha (TNF‐α), using Luminex assays in 109 preoperative DBS PD patients, 49 postoperative DBS PD patients, and 113 age‐ and sex‐matched controls. The plasma protein data of the different groups were then statistically analyzed. Results: RANTES (p < 0.001) and TNF‐α (p = 0.005) levels differed significantly between the three groups. A strong and significant correlation between RANTES levels and Hoehn‐Yahr (H‐Y) stage was observed in preoperative PD patients (rs = 0.567, p < 0.001). Significant correlations between RANTES levels and Unified Parkinson's Disease Rating Scale III (UPDRS III) score (rs1 = 0.644, p = 0.033 and rs2 = 0.620, p = 0.042) were observed in matched patients. No correlation was observed for TNF‐α levels. Conclusion: The results of this study indicate that PD patients have a persistent inflammatory profile, possibly via recruitment of activated monocytes, macrophages, and T lymphocytes to the central nervous system (CNS). DBS was shown to have a significant therapeutic effect on PD, which may arise by improving the inflammatory environment of the central nervous system. [ABSTRACT FROM AUTHOR]

Aims Decreased baroreflex sensitivity is associated with poor outcome in many cardiovascular diseases including stroke, but the molecular mechanism underlying this relationship is unclear. This work was designed to test the hypothesis that acetylcholine ( ACh) and α7 nicotinic ACh receptor (α7n ACh R) mediate the protection of arterial baroreflex against stroke. Methods Sinoaortic denervation ( SAD) was used to impair the function of arterial baroreflex, and anticholinesterase agents were used to activate the cholinergic system and increase endogenous ACh. Middle cerebral artery occlusion ( MCAO) was performed in the α7n ACh R knockout ( KO) mice and Sprague- Dawley rats. Results We found decreased expression of vesicular ACh transporter ( VACh T) and α7n ACh R in rat brain after SAD. In rats subjected to MCAO, neostigmine significantly reduced the infarct size. The protective effects of neostigmine were abolished by selective n ACh R antagonist vecuronium but not by m ACh R antagonist anisodamine. In addition, the effect of neostigmine disappeared in α7n ACh R KO mice. In cultured neurons, ACh inhibited cell death induced by H2 O2. In cultured microglial cells, ACh decreased the release of proinflammatory cytokines induced by lipopolysaccharide. These in vitro effects were blocked by selective α7n ACh R antagonists. Conclusion Taken together, these findings indicate that the ACh-α7n ACh R involved in the protective effects of arterial baroreflex against ischemic stroke. [ABSTRACT FROM AUTHOR]