Deep brain stimulation improves central nervous system inflammation in Parkinson's disease: Evidence and perspectives

Abstract

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 (r_s = 0.567, p < 0.001). Significant correlations between RANTES levels and Unified Parkinson's Disease Rating Scale III (UPDRS III) score (r_s1 = 0.644, p = 0.033 and r_s2 = 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.

Keywords: Parkinson's disease; RANTES; TNF-α; deep brain stimulation; immunological disturbances; inflammation.