Misdirection of Regenerating Motor Axons After Nerve Injury and Repair in the Rat Sciatic Nerve Model

Overview

Journal Exp Neurol

Specialty Neurology

Date 2008 May 2

PMID 18448099

Citations 39

Authors

Godard C W de Ruiter

Martijn J A Malessy

Awad O Alaid

Robert J Spinner

JaNean K Engelstad

E J Sorenson

K R Kaufman

Peter J Dyck

Anthony J Windebank

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Exosomes: new targets for understanding axon guidance in the developing central nervous system.

Liu M, Teng T Front Cell Dev Biol. 2025; 12():1510862.

PMID: 39850798 PMC: 11754257. DOI: 10.3389/fcell.2024.1510862.

Brief Electrical Stimulation Promotes Recovery after Surgical Repair of Injured Peripheral Nerves.

Gordon T Int J Mol Sci. 2024; 25(1).

PMID: 38203836 PMC: 10779324. DOI: 10.3390/ijms25010665.

Treadmill training of rats after sciatic nerve graft does not alter accuracy of muscle reinnervation.

Barham M, Andermahr J, Majczynski H, Slawinska U, Vogt J, Neiss W Front Neurol. 2023; 13:1050822.

PMID: 36742044 PMC: 9893025. DOI: 10.3389/fneur.2022.1050822.

Repair of Long Peripheral Nerve Defects in Sheep: A Translational Model for Nerve Regeneration.

Contreras E, Traserra S, Bolivar S, Fores J, Jose-Cunilleras E, Delgado-Martinez I Int J Mol Sci. 2023; 24(2).

PMID: 36674848 PMC: 9863630. DOI: 10.3390/ijms24021333.

The Effect of Electrical Stimulation on Nerve Regeneration Following Peripheral Nerve Injury.

Juckett L, Saffari T, Ormseth B, Senger J, Moore A Biomolecules. 2022; 12(12).

PMID: 36551285 PMC: 9775635. DOI: 10.3390/biom12121856.

References

Dyck P, LAMBERT E, Wood M, Linscheid R . Assessment of nerve regeneration and adaptation after median nerve reconnection and digital neurovascular flap transfer. Neurology. 1988; 38(10):1586-91. DOI: 10.1212/wnl.38.10.1586. View

Varejao A, Cabrita A, Meek M, Bulas-Cruz J, Filipe V, Gabriel R . Ankle kinematics to evaluate functional recovery in crushed rat sciatic nerve. Muscle Nerve. 2003; 27(6):706-14. DOI: 10.1002/mus.10374. View

Meyer R, Moskovitz A, Abrams R, Botte M . Inaccurate projection of rat soleus motoneurons: a comparison of nerve repair techniques. Muscle Nerve. 1997; 20(1):29-37. DOI: 10.1002/(sici)1097-4598(199701)20:1<29::aid-mus4>3.0.co;2-j. View

Swett J, Wikholm R, Blanks R, Swett A, Conley L . Motoneurons of the rat sciatic nerve. Exp Neurol. 1986; 93(1):227-52. DOI: 10.1016/0014-4886(86)90161-5. View

Sulaiman O, Midha R, Munro C, Matsuyama T, Al-Majed A, Gordon T . Chronic Schwann cell denervation and the presence of a sensory nerve reduce motor axonal regeneration. Exp Neurol. 2002; 176(2):342-54. DOI: 10.1006/exnr.2002.7928. View

Bernstein J, Guth L . Nonselectivity in establishment of neuromuscular connections following nerve regeneration in the rat. Exp Neurol. 1961; 4:262-75. DOI: 10.1016/0014-4886(61)90047-4. View

Evans P, Bain J, Mackinnon S, Makino A, Hunter D . Selective reinnervation: a comparison of recovery following microsuture and conduit nerve repair. Brain Res. 1991; 559(2):315-21. DOI: 10.1016/0006-8993(91)90018-q. View

Robinson G, Madison R . Developmentally regulated changes in femoral nerve regeneration in the mouse and rat. Exp Neurol. 2005; 197(2):341-6. DOI: 10.1016/j.expneurol.2005.10.007. View

Brushart T, Mesulam M . Alteration in connections between muscle and anterior horn motoneurons after peripheral nerve repair. Science. 1980; 208(4444):603-5. DOI: 10.1126/science.7367884. View

10.

Puigdellivol-Sanchez A, Prats-Galino A, RUANO-GIL D, Molander C . Fast blue and diamidino yellow as retrograde tracers in peripheral nerves: efficacy of combined nerve injection and capsule application to transected nerves in the adult rat. J Neurosci Methods. 2000; 95(2):103-10. DOI: 10.1016/s0165-0270(99)00164-8. View

11.

Mackinnon S, Dellon A, OBrien J . Changes in nerve fiber numbers distal to a nerve repair in the rat sciatic nerve model. Muscle Nerve. 1991; 14(11):1116-22. DOI: 10.1002/mus.880141113. View

12.

Lutz B . The role of a barrier between two nerve fascicles in adjacency after transection and repair of a peripheral nerve trunk. Neurol Res. 2004; 26(4):363-70. DOI: 10.1179/016164104225013725. View

13.

Brooke M, Kaiser K . Some comments on the histochemical characterization of muscle adenosine triphosphatase. J Histochem Cytochem. 1969; 17(6):431-2. DOI: 10.1177/17.6.431. View

14.

Abernethy D, Rud A, Thomas P . Neurotropic influence of the distal stump of transected peripheral nerve on axonal regeneration: absence of topographic specificity in adult nerve. J Anat. 1992; 180 ( Pt 3):395-400. PMC: 1259641. View

15.

Puigdellivol-Sanchez A, Prats-Galino A, Molander C . Estimations of topographically correct regeneration to nerve branches and skin after peripheral nerve injury and repair. Brain Res. 2006; 1098(1):49-60. DOI: 10.1016/j.brainres.2006.04.077. View

16.

Puigdellivol-Sanchez A, Prats-Galino A, Ruano-Gil D, Molander C . Persistence of tracer in the application site--a potential confounding factor in nerve regeneration studies. J Neurosci Methods. 2003; 127(1):105-10. DOI: 10.1016/s0165-0270(03)00128-6. View

17.

Gorio A, Carmignoto G, Finesso M, Polato P, Nunzi M . Muscle reinnervation--II. Sprouting, synapse formation and repression. Neuroscience. 1983; 8(3):403-16. DOI: 10.1016/0306-4522(83)90188-4. View

18.

Witzel C, Rohde C, Brushart T . Pathway sampling by regenerating peripheral axons. J Comp Neurol. 2005; 485(3):183-90. DOI: 10.1002/cne.20436. View

19.

Miledi R, Stefani E . Non-selective re-innervation of slow and fast muscle fibres in the rat. Nature. 1969; 222(5193):569-71. DOI: 10.1038/222569a0. View

20.

de Medinaceli L . Functional consequences of experimental nerve lesions: effects of reinnervation blend. Exp Neurol. 1988; 100(1):166-78. DOI: 10.1016/0014-4886(88)90209-9. View