Epidural oscillating field stimulation increases axonal regenerative capacity and myelination after spinal cord trauma

Oscillating field stimulation (OFS) with regular alterations in the polarity of electric current is a unique, experimental approach to stimulate, support, and potentially guide the outgrowth of both sensory and motor nerve fibers after spinal cord injury (SCI). In previous experiments, we demonstrated the beneficial effects of OFS in a 4-week survival period after SCI. In this study, we observed the major behavioral, morphological, and protein changes in rats after 15 minutes of T9 spinal compression with a 40 g force, followed by long-lasting OFS (50 µA), over a 8-week survival period. Three groups of rats were analyzed: rats after T9 spinal compression (SCI group); SCI rats subjected to implantation of active oscillating field stimulator (OFS + SCI group); and SCI rats subjected to nonfunctional OFS (nOFS + SCI group). Histopathological analysis of spinal tissue indicated a strong impact of epidural OFS on the reduction of tissue and myelin loss after SCI in the segments adjacent to the lesion site. Quantitative fluorescent analysis of the most affected areas of spinal cord tissue revealed a higher number of spared axons and oligodendrocytes of rats in the OFS + SCI group, compared with rats in the SCI and nOFS + SCI groups. The protein levels of neurofilaments (NF-l), growth-associated protein-43 (marker for newly sprouted axons), and myelin basic protein in rats were signifiantly increased in the OFS + SCI group than in the nOFS + SCI and SCI groups. This suggests a supporting role of the OFS in axonal and myelin regeneration after SCI. Moreover, rats in the OFS + SCI group showed great improvements in sensory and motor functions than did rats in the nOFS + SCI and SCI groups. All these findings suggest that long-lasting OFS applied immediately after SCI can provide a good microenviroment for recovery of damaged spinal tissue by triggering regenreative processes in the acute phase of injury.