TY - JOUR
T1 - Electrical stimulation restores the specificity of sensory axon regeneration
AU - Brushart, Thomas M.
AU - Jari, Rajesh
AU - Verge, Valerie
AU - Rohde, Charles
AU - Gordon, Tessa
N1 - Funding Information:
Supported by NIH RO1 NS034484-07. The authors thank Katherine Weaver for artwork and Pamela Talalay for editing the manuscript. This paper is dedicated to the memory of Mr. Phillip Kessens, whose invaluable technical assistance made this and many similar projects possible.
PY - 2005/7
Y1 - 2005/7
N2 - Electrical stimulation at the time of nerve repair promotes motoneurons to reinnervate appropriate pathways leading to muscle [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 stimulates sensory neurons to regenerate [Geremia, N.M., Gordon, T., Al-Majed, A.A., Brushart, T.M., Verge, V.M., 2002. Brief electrical stimulation promotes regeneration of sensory fibers into cutaneous and muscle branches of femoral nerve. Neurosci. Abstr. 535.14]. The present experiments examine the effects of electrical stimulation on the specificity of sensory axon regeneration. The unoperated rat femoral cutaneous branch is served by 2-3 times more DRG neurons than is the muscle branch [Brushart, T.M., 1988. Preferential reinnervation of motor nerves by regenerating motor axons. J. Neurosci. 8, 1026-1031]. After transection and repair of the femoral trunk, equal numbers of DRG neurons project to both branches. However, 1 h of electrical stimulation restores the normal proportion of DRG neurons reinnervating skin and muscle. To ask if the redistribution of stimulated neurons results from enhanced specificity of target reinnervation, we developed a new technique of sequential double labeling. DRG neurons projecting to the femoral muscle branch were prelabeled with Fluoro Gold 2 weeks before the nerve was transected proximally and repaired with or without 1 h of 20-Hz electrical stimulation. Three weeks after repair, the muscle nerve was labeled a second time with Fluororuby. The percentage of regenerating neurons that both originally served muscle and returned to muscle after nerve repair increased from 40% without stimulation to 75% with stimulation. Electrical stimulation thus dramatically alters the distribution of regenerating sensory axons, replacing normally random behavior with selective reinnervation of tissue-specific targets. If the enhanced regeneration specificity resulting from electrical stimulation is found to improve function in a large animal model, this convenient and safe technique may be a useful adjunct to clinical nerve repair.
AB - Electrical stimulation at the time of nerve repair promotes motoneurons to reinnervate appropriate pathways leading to muscle [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 stimulates sensory neurons to regenerate [Geremia, N.M., Gordon, T., Al-Majed, A.A., Brushart, T.M., Verge, V.M., 2002. Brief electrical stimulation promotes regeneration of sensory fibers into cutaneous and muscle branches of femoral nerve. Neurosci. Abstr. 535.14]. The present experiments examine the effects of electrical stimulation on the specificity of sensory axon regeneration. The unoperated rat femoral cutaneous branch is served by 2-3 times more DRG neurons than is the muscle branch [Brushart, T.M., 1988. Preferential reinnervation of motor nerves by regenerating motor axons. J. Neurosci. 8, 1026-1031]. After transection and repair of the femoral trunk, equal numbers of DRG neurons project to both branches. However, 1 h of electrical stimulation restores the normal proportion of DRG neurons reinnervating skin and muscle. To ask if the redistribution of stimulated neurons results from enhanced specificity of target reinnervation, we developed a new technique of sequential double labeling. DRG neurons projecting to the femoral muscle branch were prelabeled with Fluoro Gold 2 weeks before the nerve was transected proximally and repaired with or without 1 h of 20-Hz electrical stimulation. Three weeks after repair, the muscle nerve was labeled a second time with Fluororuby. The percentage of regenerating neurons that both originally served muscle and returned to muscle after nerve repair increased from 40% without stimulation to 75% with stimulation. Electrical stimulation thus dramatically alters the distribution of regenerating sensory axons, replacing normally random behavior with selective reinnervation of tissue-specific targets. If the enhanced regeneration specificity resulting from electrical stimulation is found to improve function in a large animal model, this convenient and safe technique may be a useful adjunct to clinical nerve repair.
KW - Afferent
KW - Axonal transport
KW - Dorsal root ganglion
KW - Muscle
KW - Peripheral nerve
KW - Reinnervation
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U2 - 10.1016/j.expneurol.2005.02.007
DO - 10.1016/j.expneurol.2005.02.007
M3 - Article
C2 - 15899259
AN - SCOPUS:19344377230
SN - 0014-4886
VL - 194
SP - 221
EP - 229
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -