Misdirection of regenerating motor axons after nerve injury and repair in the rat sciatic nerve model

• Published in: Experimental neurology 2008-06, Vol.211 (2), p.339-350
• Main Authors: de Ruiter, Godard C.W., Malessy, Martijn J.A., Alaid, Awad O., Spinner, Robert J., Engelstad, JaNean K., Sorenson, E.J., Kaufman, K.R., Dyck, Peter J., Windebank, Anthony J.
• Format: Article
• Language: English
• Subjects: Aberrant reinnervation; Accuracy of regeneration; Action Potentials - physiology; Animals; Ankle motion analysis; Axons - physiology; Biological and medical sciences; Disease Models, Animal; Double labeling; Injuries of the nervous system and the skull. Diseases due to physical agents; Medical sciences; Motor Neurons - physiology; Nerve Regeneration - physiology; Neurology; Rats; Rats, Sprague-Dawley; Recovery of Function - physiology; Sciatic Neuropathy - physiopathology; Sciatic Neuropathy - surgery; Sequential retrograde tracing; Traumas. Diseases due to physical agents
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2007.12.023

Misdirection of regenerating axons is one of the factors that can explain the poor results often found after nerve injury and repair. In this study, we quantified the degree of misdirection and the effect on recovery of function after different types of nerve injury and repair in the rat sciatic nerve model; crush injury, direct coaptation, and autograft repair. Sequential tracing with retrograde labeling of the peroneal nerve before and 8 weeks after nerve injury and repair was performed to quantify the accuracy of motor axon regeneration. Digital video analysis of ankle motion was used to investigate the recovery of function. In addition, serial compound action potential recordings and nerve and muscle morphometry were performed. In our study, accuracy of motor axon regeneration was found to be limited; only 71% (± 4.9%) of the peroneal motoneurons were correctly directed 2 months after sciatic crush injury, 42% (± 4.2%) after direct coaptation, and 25% (± 6.6%) after autograft repair. Recovery of ankle motion was incomplete after all types of nerve injury and repair and demonstrated a disturbed balance of ankle plantar and dorsiflexion. The number of motoneurons from which axons had regenerated was not significantly different from normal. The number of myelinated axons was significantly increased distal to the site of injury. Misdirection of regenerating motor axons is a major factor in the poor recovery of nerves that innervate different muscles. The results of this study can be used as basis for developing new nerve repair techniques that may improve the accuracy of regeneration.