title: Brief electrical stimulation improves nerve regeneration after delayed repair in Sprague Dawley rats.
abstract: 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.
authors.affiliation: Division of Plastic Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Kate
authors.initials: K
authors.lastname: Elzinga
authors.affiliation: Center for Neuroscience, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Neil
authors.initials: N
authors.lastname: Tyreman
authors.affiliation: Division of Plastic Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Adil
authors.initials: A
authors.lastname: Ladak
authors.affiliation: Division of Plastic Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Bohdan
authors.initials: B
authors.lastname: Savaryn
authors.affiliation: Division of Plastic Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jaret
authors.initials: J
authors.lastname: Olson
authors.affiliation: Center for Neuroscience, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada. Electronic address: tessat.gordon@gmail.com.
authors.forename: Tessa
authors.initials: T
authors.lastname: Gordon
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology* / Q000502:physiology; D019771:Axotomy / Q000379:methods; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D009046:Motor Neurons / Q000502:physiology; D009121:Muscle Denervation / Q000379:methods; D009414:Nerve Growth Factors / Q000494:pharmacology; D009416:Nerve Regeneration / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000378:metabolism / Q000628:therapy*; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D012583:Schwann Cells / Q000378:metabolism; D013997:Time Factors
chemical_list: D009414:Nerve Growth Factors
keywords: Brief electrical stimulation; Chronic Schwann cell denervation; Chronic neuronal axotomy; Delayed nerve repair; Peripheral nerve regeneration