Oscillating field stimulation promotes recovery from spinal cord injury in rats by regulating the differentiation of endogenous neural stem cells.

Abstract

The mammalian spinal cord (SC) has a limited self-repair capacity and exogenous treatments are yet to produce substantial functional recovery following SC injury (SCI). The SC contains endogenous neural stem cells (NSCs) with multi-lineage differentiation potential and it may be possible to restore function via interventions that promote NSC differentiation following SCI. Oscillating field stimulation (OFS) has been reported to regulate the Wnt signaling pathway, a known modulator of NSC differentiation. However, the effects of OFS on NSC differentiation following SCI and associated functional recovery have not been previously examined. In the current study, the Basso-Beattie-Bresnahan (BBB) score was used to assess locomotion recovery following SCI in rats and immunofluorescence double-staining was used to examine the regeneration of neurons and oligodendrocytes derived from NSCs. Furthermore, Nissl staining was performed to assess the viability and survival of neurons following SCI, while recovery of the myelin sheath was examined by uranium-lead staining under transmission electron microscopy. OFS delivered via an implanted stimulator enhanced the differentiation of NSCs into neurons and oligodendrocytes and accelerated the regeneration of myelinated axons. Additionally, BBB scores revealed superior locomotion recovery in OFS-treated rats compared with SCI controls. Collectively, these results indicated that OFS may be a feasible strategy to promote SCI recovery by regulating the differentiation of endogenous NSCs.