title: Electrical stimulation promotes sensory neuron regeneration and growth-associated gene expression.
abstract: Brief electrical stimulation enhances the regenerative ability of axotomized motor [Nix, W.A., Hopf, H.C., 1983. Electrical stimulation of regenerating nerve and its effect on motor recovery. Brain Res. 272, 21-25; Al-Majed, A.A., Neumann, C.M., Brushart, T.M., Gordon, T., 2000. Brief electrical stimulation promotes the speed and accuracy of motor axonal regeneration. J. Neurosci. 20, 2602-2608] and sensory [Brushart, T.M., Jari, R., Verge, V., Rohde, C., Gordon, T., 2005. Electrical stimulation restores the specificity of sensory axon regeneration. Exp. Neurol. 194, 221-229] neurons. Here we examined the parameter of duration of stimulation on regenerative capacity, including the intrinsic growth programs, of sensory neurons. The effect of 20 Hz continuous electrical stimulation on the number of DRG sensory neurons that regenerate their axons was evaluated following transection and surgical repair of the femoral nerve trunk. Stimulation was applied proximal to the repair site for 1 h, 3 h, 1 day, 7 days or 14 days at the time of nerve repair. Following a 21-day regeneration period, DRG neurons that regenerated axons into the muscle and cutaneous sensory nerve branches were retrogradely identified. Stimulation of 1 h led to a significant increase in DRG neurons regenerating into cutaneous and muscle branches when compared to 0 h (sham) stimulation or longer periods of stimulation. Stimulation for 1 h also significantly increased the numbers of neurons that regenerated axons beyond the repair site 4 days after lesion and was correlated with a significant increase in expression of growth-associated protein 43 (GAP-43) mRNA in the regenerating neurons at 2 days post-repair. An additional indicator of heightened plasticity following 1 h stimulation was elevated expression of brain-derived neurotrophic factor (BDNF). The effect of brief stimulation on enhancing sensory and motoneuron regeneration holds promise for inducing improved peripheral nerve repair in the clinical setting.
authors.affiliation: Department of Anatomy and Cell Biology, Cameco MS/Neuroscience Research Center University of Saskatchewan, Saskatoon City Hospital, Saskatchewan, Canada.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Geremia
authors.forename: Tessa
authors.initials: T
authors.lastname: Gordon
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Brushart
authors.forename: Abdulhakeem A
authors.initials: AA
authors.lastname: Al-Majed
authors.forename: Valerie M K
authors.initials: VM
authors.lastname: Verge
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D051700:Activating Transcription Factor 3 / Q000378:metabolism; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D004558:Electric Stimulation; D005260:Female; D005267:Femoral Nerve / Q000166:cytology / Q000502:physiology; D019922:GAP-43 Protein / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009416:Nerve Regeneration / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D016707:Tissue Fixation
chemical_list: D051700:Activating Transcription Factor 3; D000779:Anesthetics, Local; C497108:Atf3 protein, rat; D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D013779:Tetrodotoxin