Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats

• Published in: Experimental neurology Vol. 269; pp. 142 - 153
• Main Authors: Elzinga, Kate, Tyreman, Neil, Ladak, Adil, Savaryn, Bohdan, Olson, Jaret, Gordon, Tessa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2015
• Subjects: Animals; Axons - pathology; Axons - physiology; Axotomy - methods; Brief electrical stimulation; Chronic neuronal axotomy; Chronic Schwann cell denervation; Delayed nerve repair; Electric Stimulation - methods; Female; Motor Neurons - physiology; Muscle Denervation - methods; Nerve Growth Factors - pharmacology; Nerve Regeneration - physiology; Peripheral Nerve Injuries - metabolism; Peripheral Nerve Injuries - therapy; Peripheral nerve regeneration; Rats, Sprague-Dawley; Recovery of Function - physiology; Schwann Cells - metabolism; Time Factors; Chronic neuronal axotomy; Peripheral nerve regeneration; Delayed nerve repair; Brief electrical stimulation; Chronic Schwann cell denervation
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2015.03.022

Functional recovery after peripheral nerve injury and surgical repair declines with time and distance because the injured neurons without target contacts (chronic axotomy) progressively lose their regenerative capacity and chronically denervated Schwann cells (SCs) atrophy and fail to support axon regeneration. Findings that brief low frequency electrical stimulation (ES) accelerates axon outgrowth and muscle reinnervation after immediate nerve surgery in rats and human patients suggest that ES might improve regeneration after delayed nerve repair. To test this hypothesis, common peroneal (CP) neurons were chronically axotomized and/or tibial (TIB) SCs and ankle extensor muscles were chronically denervated by transection and ligation in rats. The CP and TIB nerves were cross-sutured after three months and subjected to either sham or one hour 20Hz ES. Using retrograde tracing, we found that ES significantly increased the numbers of both motor and sensory neurons that regenerated their axons after a three month period of chronic CP axotomy and/or chronic TIB SC denervation. Muscle and motor unit forces recorded to determine the numbers of neurons that reinnervated gastrocnemius muscle demonstrated that ES significantly increased the numbers of motoneurons that reinnervated chronically denervated muscles. We conclude that electrical stimulation of chronically axotomized motor and sensory neurons is effective in accelerating axon outgrowth into chronically denervated nerve stumps and improving target reinnervation after delayed nerve repair. Possible mechanisms for the efficacy of ES in promoting axon regeneration and target reinnervation after delayed nerve repair include the upregulation of neurotrophic factors. •Recovery of function is poor after delayed peripheral nerve repair surgery.•Repaired rat nerves were stimulated for 1h at 20Hz after immediate or delayed nerve repair.•ES promoted nerve regeneration and muscle reinnervation after immediate and delayed nerve repair.•ES may readily be applied to human nerve surgery to improve functional recovery.