Electrical stimulation promotes functional recovery after spinal cord injury by activating endogenous spinal cord-derived neural stem/progenitor cell: an in vitro and in vivo study

Abstract

Background context

Electrical stimulation is a noninvasive treatment method that has gained popularity in the treatment of spinal cord injury (SCI). Activation of spinal cord-derived neural stem/progenitor cell (SC-NSPC) proliferation and differentiation in the injured spinal cord may elicit considerable neural regenerative effects.

Purpose

This study aimed to explore the effect of electrical stimulation on the neurogenesis of SC-NSPCs.

Study design

This study analyzed the effects of electrical stimulation on neurogenesis in rodent SC-NSPCs in vitro and in vivo and evaluated functional recovery and neural circuitry improvements with electrical stimulation using a rodent SCI model.

Methods

Rats (20 rats/group) were assigned to sham (Group 1), SCI only (Group 2), SCI + electrode implant without stimulation (Group 3), and SCI + electrode with stimulation (Group 4) groups to count total SC-NSPCs and differentiated neurons and to evaluate morphological changes in differentiated neurons. Furthermore, the Basso, Beattie, and Bresnahan scores were analyzed, and the motor- and somatosensory-evoked potentials in all rats were monitored.

Results

Biphasic electrical currents enhanced SC-NSPC proliferation differentiation and caused qualitative morphological changes in differentiated neurons in vitro. Electrical stimulation promoted SC-NSPC proliferation and neuronal differentiation and improved functional outcomes and neural circuitry in SCI models. Increased Wnt3, Wnt7, and β-catenin protein levels were also observed after electrical stimulation.

Conclusions

Our study proved the beneficial effects of electrical stimulation on SCI. The Wnt/β-catenin pathway activation may be associated with this relationship between electrical stimulation and neuronal regeneration after SCI.

Clinical significance

The study confirmed the benefits of electrical stimulation on SCI based on cellular, functional, electrophysiological, and histological evidence. Based on these findings, we expect electrical stimulation to make a positive and significant difference in SCI treatment strategies.