Dynamic impact of brief electrical nerve stimulation on the neural immune axis-polarization of macrophages toward a pro-repair phenotype in demyelinated peripheral nerve.

摘要: Demyelinating peripheral nerves are infiltrated by cells of the monocyte lineage, including macrophages, which highly plastic, existing on a continuum from pro-inflammatory M1 to pro-repair M2 phenotypic states. Whether one can therapeutically manipulate demyelinated promote phenotype remains be elucidated. We previously identified brief electrical nerve stimulation (ES) as beneficial for remyelination, benefits include accelerated clearance making us theorize that ES alters local immune response. Thus, impact microenvironment in zone demyelination was examined. Adult male rat tibial were focally via 1% lysophosphatidyl choline (LPC) injection. Five days later, half underwent 1 hour 20 Hz sciatic proximal LPC injection site. had remarkable and significant impact, shifting macrophage predominantly pro-inflammatory/M1 toward pro-repair/M2 one, evidenced an increased incidence expression M2-associated markers macrophages decrease M1-associated marker expression. This discernible at 3 post-ES (8 post-LPC) continued 5 day (10 time point also affected chemokine (C-C motif) ligand 2 (CCL2; aka MCP-1) manner correlated with increases decreases numbers observed zone. The data establish briefly increasing neuronal activity favorably nerve, rapidly polarizing phenotype, therapeutic concept may extend other pathologies. GLIA 2016;64:1546-1561.