DEPOLARIZATION AND ELECTRICAL STIMULATION ENHANCE IN VITRO AND IN VIVO SENSORY AXON GROWTH AFTER SPINAL CORD INJURY

Exp Neurol, 2018 · DOI: 10.1016/j.expneurol.2017.11.011 · Published: February 1, 2018

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates how neuronal activity, specifically through electrical stimulation (ES), can influence the regrowth of nerve fibers (axons) after spinal cord injury (SCI). The research explores whether ES can trigger regenerative processes in the injured central nervous system (CNS). The study uses KCl-induced depolarization in cell cultures, in vivo ES followed by ex-vivo neurite growth assays, and ES after spinal cord lesions and cell grafting to identify factors that enhance neurite growth and axonal regeneration. The findings suggest that ES has time-dependent effects on the ability of sensory neurons to regenerate and may improve axonal regeneration when combined with other treatments for SCI.

Study Duration

4 weeks

Participants

107 adult female Fischer 344 rats

Evidence Level

Not specified

Key Findings

1
KCl-induced depolarization can either inhibit or enhance neurite growth of DRG neurons depending on the duration and timing of the exposure.
2
The increases in neurite growth after electrical stimulation depend on a delay of more than 1 day between the stimulation and assessing growth.
3
Electrical stimulation in vivo enhances axon growth into a cellular graft after spinal cord injury, suggesting a potential therapeutic effect.

Research Summary

The study examined the effects of neuronal activity, induced by KCl depolarization and electrical stimulation (ES), on axonal regeneration after spinal cord injury (SCI). In vitro experiments showed that the timing and duration of KCl exposure significantly influenced neurite growth, with short-term depolarization or delayed replating after extended exposure promoting growth. In vivo, ES enhanced the growth of sensory axons into a cellular graft after SCI, although it did not lead to sensory functional recovery. The study suggests ES can modulate the regenerative capacity of sensory neurons.

Practical Implications

Therapeutic Potential

Electrical stimulation shows promise as a therapeutic strategy to enhance axonal regeneration after spinal cord injury. It needs to be combined with other therapies.

Timing is Crucial

The timing and duration of electrical stimulation are critical factors in determining its effectiveness in promoting nerve regeneration.

Further Optimization Needed

Further research is needed to optimize the parameters of electrical stimulation, such as frequency and intensity, and to understand its mechanisms of action for clinical applications.

Study Limitations

1
Cuff electrodes can result in thickening of epineurium and ingrowth of endometrial connective tissue.
2
The cuffs used in this study were designed to avoid compression by leaving sufficient space around the nerve, chronically implanted cuffs were enclosed by connective tissue.
3
Recovery of sensory function did not differ between animals that underwent ES and sham, a finding that is not surprising without guidance and growth stimulation of dorsal column sensory axons across the lesion to form appropriate synapses with their target.

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