Abstract

Electrical stimulation (ES) therapy has good effects in patients with nervous system injury-related diseases. ES promotes nerve cell regeneration and stimulates Schwann cells to express neurotrophic factors. The incidence of stress urinary incontinence (SUI) among elderly people is increasing. Some studies suggest that damage to the pudendal nerve is closely related to the pathogenesis of SUI. It has also been found that pelvic ES can reduce SUI symptoms in a rat model of SUI caused by pudendal nerve injury. Clinically, pelvic floor electrical stimulation is effective in patients with mild to moderate SUI. These studies indicate that ES may ameliorate damage to the pudendal nerve and thus achieve the goal of SUI treatment, although the mechanism of action of this treatment remains unclear. Therefore, the purpose of the present study was to clarify the relationships among ES, neural cells and Schwann cells at the cellular level. We applied ES to nerve cells at 100 mV/mm or 200 mV/mm for 0, 0.5, 1, or 2 h to investigate changes in nerve cell activity. We then co-cultured the nerve cells with Schwann cells to explore the influence of single-culture and co-culture conditions on the nerve cells. Compared to non-ES, ES of the nerve cells increased their activity. Compared to those in single culture, co-cultured nerve cells exhibited an additional increase in activity. We also found that Schwann cell derived exosomes could promote the activity of nerve cells, with glutamate and calcium ions playing a potential role in this process. These results suggest that the mutual regulation of neural cells and Schwann cells plays an important role in the process by which ES ameliorates neurological function, which may provide a basis for subsequent studies.

Highlights

  • Electrical stimulation (ES) therapy plays an important role in delaying muscle atrophy in hemiplegic patients and promoting neuromuscular function recovery and has beneficial effects in patients with nervous system injury-related diseases[1,2,3,4,5]

  • The optical density values at each time point (0 h, 0.5 h, 1 h, and 2 h) for the Sham ES group were 1.000 ± 0.114, 0.993 ± 0.057, 0.991 ± 0.075, and 0.996 ± 0.053, respectively, with the 0 h group used for standardization, and there were no significant differences among groups (p > 0.05)

  • The results showed that the intracellular calcium concentration of Schwann cells reached its highest value at 100 μmol/L, which is consistent with the change in exosome secretion

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Summary

Introduction

Electrical stimulation (ES) therapy plays an important role in delaying muscle atrophy in hemiplegic patients and promoting neuromuscular function recovery and has beneficial effects in patients with nervous system injury-related diseases[1,2,3,4,5]. Studies have demonstrated that Schwann cells begin to highly express neurotrophic factors after ES, and these factors are continuously released to the injured nerves, improving the nerve regeneration microenvironment, creating a good platform for nerve repair[8,9], and promoting axonal regeneration. Studies have suggested that Schwann cell-derived exosomes play a role in promoting nerve regeneration and repair[23]. We hypothesized that ES may repair pudendal nerve injury by increasing the activity of nerve cells via a process involving Schwann cell derived exosomes, thereby achieving the goal of treating SUI

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