Electrical Stimulation as a Conditioning Lesion for Peripheral Nerve Regeneration
Jenna-Lynn B Senger, MD1; K. Ming Chan, MD2; Jaret L Olson, MD3; Christine Webber, PhD1; (1)University of Alberta, Edmonton, AB, Canada, (2)Division of Physical Medicine & Rehabilitation, University of Alberta, Edmonton, AB, Canada, (3)Division of Plastic Surgery, University of Alberta, Edmonton, AB, Canada
Introduction. The beneficial effects of a preinjury crush conditioning lesion (CL) on peripheral nerve regeneration have been well-documented in animal models. Despite this, no human studies have been attempted to date. Principle reasons are the ethical dilemma of deliberately injuring an intact nerve and the difficulty in predicting the timing of a nerve injury. Recent studies demonstrated that 1 hour of electrical stimulation (ES) produces effects similar to CL in neuronal cultures, suggesting its role as a clinically translatable conditioning technique to enhance regeneration. This study hypothesizes that ES prior to nerve injury will enhance nerve regeneration.
Materials & Methods. Twelve Sprague-Dawley rats were equally divided into four groups based on conditioning-type to the common peroneal (CP) nerve: ES, crush, sham-ES, and naïve. Three days following conditioning, dorsal root ganglia (DRGs) were collected and stained for growth associated factor-43 (GAP-43), brain-derived neurotrophic factor (BDNF), and glial fibrillary acidic protein (GFAP). A second cohort of 24 animals, one week following conditioning, underwent a cut/coaptation of the CP nerve at the sciatic trifurcation. On post-cut day seven, to determine the extent of axon growth, nerves were collected and stained with NF200 and GFAP.
Results. Three day post-conditioning, DRGs from animals in the ES and crush groups showed significant increase in GAP-43 and BDNF expression compared to sham and naïve (p<0.001). The satellite glial cells in the DRGs from animals in the ES and crush conditioning groups showed a significant increase in GFAP expression (29.3% and 39.3% respectively) compared to sham (8.6%) and naïve (13.5%). Increased RAG expression suggests ES should improve regeneration similar to a crush conditioning. Axonal counts revealed similar lengths of regeneration between ES and crush (4.2±0.6 mm vs. 4.3±0.4 mm, p=0.66) that were superior to sham-stimulation (1.2±0.4 mm, p<0.05) and naïve (1.1±0.3 mm, p<0.05). A greater number of axons at the distal tip were present in animals that received either ES or crush conditioning compared to the unconditioned groups.
Conclusions. By demonstrating similar improvements in axon regeneration, this study suggests that ES conditioning may produce regenerative outcomes comparable to the traditional crush injury model. This opens the possibility of testing ES for conditioning-like effects in clinical trials prior to nerve surgery to enhance nerve regeneration.
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