Influence of Simulated Deep Brain Stimulation on the Expression of Inflammatory Mediators by Human Central Nervous System Cells In Vitro

Deep brain stimulation (DBS) seems to modulate inflammatory processes. Whether this modulation leads to an induction or suppression of inflammatory mediators is still controversially discussed. Most studies of the influence of electrical stimulation on inflammation were conducted in rodent models with direct current stimulation and/or long impulses, both of which differ from the pattern in DBS. This makes comparisons with the clinical condition difficult. We established an in-vitro model that simulated clinical stimulation patterns to investigate the influence of electrical stimulation on proliferation and survival of human astroglial cells, microglia, and differentiated neurons. We also examined its influence on the expression of the inflammatory mediators C-X-C motif chemokine (CXCL)12, CXCL16, CC-chemokin-ligand-2 (CCL)2, CCL20, and interleukin (IL)-1 beta and IL-6 by these cells using quantitative polymerase chain reaction. In addition, protein expression was assessed by immunofluorescence double staining. In our model, electrical stimulation did not affect proliferation or survival of the examined cell lines. There was a significant upregulation of CXCL12 in the astrocyte cell line SVGA, and of IL-1 beta in differentiated SH-SY5Y neuronal cells at both messenger RNA and protein levels. Our model allowed a valid examination of chemokines and cytokines associated with inflammation in human brain cells. With it, we detected the induction of inflammatory mediators by electrical stimulation in astrocytes and neurons.

Automated summary

Deep brain stimulation appears to modulate inflammatory processes, with controversial effects on the induction or suppression of inflammatory mediators. An in-vitro model simulating clinical stimulation patterns showed induced expression of inflammatory mediators by electrical stimulation in specific brain cell lines.