Skip to main content

Advertisement

Log in

Functional recovery improvement is related to aberrant reinnervation trimming. A comparative study using fresh or predegenerated nerve grafts

  • Original Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Experimentally predegenerated nerve grafts have been demonstrated to improve recovery. In a 12 month-long study, we compared the degree of recovery of conventional and predegenerated grafts in rat median nerve repair. To induce predegeneration the ulnar donor nerve was crushed and grafting to the median nerve was performed 2 weeks later. The day of recovery and the improvement of finger flexion strength were studied by the grasping test. At 3, 6, 9, and 12 months after surgery retrograde labeling studies and flexor carpi radialis muscle ATPase histochemistry were performed. In the predegenerated grafts, the recovery of finger flexion occurred 19.6±1.5 days after surgery and was significantly faster than that in the conventional group. Twelve months after surgery, a similar rate of 85% of grasping strength recovery in relation to the normal control rats was demonstrated for the conventional and predegenerated grafts. After grafting, a larger number of motoneurons, compared to the normal controls, were retrograde labeled in the median nerve. This surplus of retrograde labeled motoneurons in the predominantly sensory branch of the median nerve represented misdirected motor fibers. There was a time-related decrease in the number of labeled motoneurons, which correlated to functional grasping strength recovery. Muscle reinnervation induced a predominance of type I over type II muscle fibers. Forty percent of type I fibers were grouped indicating that collateral sprouting plays a prominent role during muscle reinnervation. Regeneration in predegenerated grafts was faster but the final rate of recovery was similar to conventional grafts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Agius E, Cochard P (1998) Comparison of neurite outgrowth induced by intact and injured sciatic nerves: a confocal and functional analysis. J Neurosci 18:328–338

    PubMed  CAS  Google Scholar 

  2. Angelov DN, Neiss WF, Streppel M, Andermahr J, Mader K, Stennert E (1996) Nimodipine accelerates axonal sprouting after surgical repair of rat facial nerve. J Neurosci 16:1041–1048

    PubMed  CAS  Google Scholar 

  3. Angelov DN, Skouras E, Guntinas-Lichius O, Streppel M, Popratiloff, Walther M, Klein J, Stennert E, Neiss WF (1999) Contralateral trigeminal nerve lesion reduces polyneuronal muscle innervation after facial nerve repair in rats. Europ J Neurosci 11:1369–1378

    Article  CAS  Google Scholar 

  4. Benoit P, Changeaux JP (1975) Consequences of tenotomy on the evolution of multiinnervation in developing rat soleus muscle. Brain Res 99:354–358

    Article  PubMed  CAS  Google Scholar 

  5. Bertelli JA, Ghizoni MF (2004) Contralateral motor rootlets and ipsilateral nerve transfers in brachial plexus reconstruction. J Neurosurg 101:770–778

    PubMed  Google Scholar 

  6. Bertelli JA, Mira JC (1995) The grasping test. A simple behavioral method for objective quantitative assessment of peripheral nerve regeneration in the rat. J Neurosci Methods 58:151–155

    Article  PubMed  CAS  Google Scholar 

  7. Bertelli JA, Mira JC, Pecot-Dechavassine M, Sebille A (1997) Selective motor hyperreinnervation using motor rootlet transfer: an experimental study in rat brachial plexus. J Neurosurg 87:79–84

    Article  PubMed  CAS  Google Scholar 

  8. Bertelli JA, Taleb M, Calixto JB, Mira JC, Ghizoni MF (2004) Long interpositional nerve graft consistently induces incomplete motor and sensory recovery in the rat. An experimental model to test nerve repair. J Neurosci Methods 134:75–80

    Article  PubMed  Google Scholar 

  9. Bertelli JA, Taleb M, Mira JC (1996) Muscle fiber type reorganization and behavioural functional recovery of rat median nerve repair with vascularized and conventional nerve grafts. Rest Neurol Neurosci 10:5–12

    Google Scholar 

  10. Bertelli JA, Taleb M, Mira JC, Ghizoni MF (2005) Variation in nerve autograft length increases fibre misdirection and decreases pruning effectiveness. An experimental study in the rat median nerve. Neurol Res 27:657–665

    Article  PubMed  CAS  Google Scholar 

  11. Bertelli JA, Taleb M, Mira JC, Ghizoni MF (2005) The course of aberrant reinnervation following nerve repair with fresh or denatured muscle autografts. J Peripher Nerv Syst 10:359–368

    Article  PubMed  Google Scholar 

  12. Bertelli JA, Taleb M, Saadi A, Mira JC, Pecot-Dechavassine M (1995) The rat brachial plexus and its terminal branches: an experimental model of the study of peripheral nerve regeneration. Microsurgery 16:77–85

    Article  PubMed  CAS  Google Scholar 

  13. Bontioti EN, Kanje M, Dahlin LB (2003) Regeneration and functional recovery in the upper extremity of rats after various types of nerve injuries. J Peripher Nerv Syst 8:159–168

    Article  PubMed  Google Scholar 

  14. Brooke MJ, Kaiser KK (1969) Some comments on the histochemical characterization of muscle adenosine-triphosphatase. J Histochem 17:431–432

    CAS  Google Scholar 

  15. Brushart TME (1988) Preferential reinnervation of motor nerves by regenerating motor axons. J Neurosci 8:1026–1031

    PubMed  CAS  Google Scholar 

  16. Brushart TM, Gerber J, Kessens P, Chen Y-G, Royall RM (1998) Contributions of pathway and neuron to preferential motor reinnervation. J Neurosci 18:8674–8681

    PubMed  CAS  Google Scholar 

  17. Carobi C, Brunetti O (1995) Tenotomy prevents the functional improvement of a muscle reinnervated with a chronically severed nerve. J Neurosci Res 40:343–348

    Article  PubMed  CAS  Google Scholar 

  18. Danielsen N, Kerns J, Holmquist B, Zhao Q, Lundborg G, Kanje M (1994) Pre-degenerated nerve grafts enhance regeneration by shorting the initial delay period. Brain Res 666:250–254

    Article  PubMed  CAS  Google Scholar 

  19. Desypris G, Parry DJ (1990) Relative efficacy of slow and fast alpha-motoneurons to reinnervate mouse soleus muscle. Am J Physiol 258:62–70

    Google Scholar 

  20. Donahue SP, English AW (1989) Selective elimination of cross-compartmental innervation in rat lateral gastrocnemius muscle. J Neurosci 9:1621–1627

    PubMed  CAS  Google Scholar 

  21. Gordon T, Yang JF, Ayer K, Stein RB, Tyreman N (1993) Recovery potential of muscle after partial denervation: a comparison between rats and humans. Brain Res Bull 30:477–482

    Article  PubMed  CAS  Google Scholar 

  22. Grow WA, Kendall-Wassmuth E, Ulibarri C, Laskowski MB (1995) Differential delay of reinnervating axons alters specificity in the rat serratus anterior muscle. J Neurobiol 4:553–562

    Article  Google Scholar 

  23. Gulati A (1996) Peripheral nerve regeneration through short-and long-term degenerated nerve transplants. Brain Res 742:265–270

    Article  PubMed  CAS  Google Scholar 

  24. Heumann R, Korshching S, Bandtlow C (1987) Changes of nerve growth factor synthetis in nonneuronal cells in response to sciatic nerve transection. J Cell Biol 104:1623–1631

    Article  PubMed  CAS  Google Scholar 

  25. Heumann R (1987) Regulation of the synthesis of nerve growth factor. J Exp Biol 132:133–150

    PubMed  CAS  Google Scholar 

  26. Ijkema-Paassen J, Meek MF, Gramsbergen A (2002) Reinnervation of muscles after transection of the sciatic nerve in adult rats. Muscle Nerve 25:891–897

    Article  PubMed  Google Scholar 

  27. Karpati G, Engel WK (1968) “Type Grouping” in skeletal muscles after experimental reinnervation. Neurology 18:447–455

    PubMed  CAS  Google Scholar 

  28. Kerns JM, Danielsen N, Holquist B, Kanje M, Lundborg G (1993) The influence of predegeneration on regeneration through peripheral nerve grafts in the rat. Exp Neurol 122:28–36

    Article  PubMed  CAS  Google Scholar 

  29. Lewin-Kowalik J, Sieron AL, Krause M, Barski JJ, Gorka D (1992) The influence of peripheral nerve graft’s predegeneration stage on the regrowth of hippocampal injured neurites and concomitant changes in submicrosomal fraction proteins of grafts. Acta Physiol Hung 79:219–231

    PubMed  CAS  Google Scholar 

  30. Millesi H (1973) Microsurgery of the peripheral nerves. Hand 5: 157–161

    Article  PubMed  CAS  Google Scholar 

  31. Mira JC (1982) Muscle changes during reinnervation after repeated nerve injuries. Reprod Nutr Dev 22B:251–260

    Google Scholar 

  32. Muller HW, Stoll G (1998) Nerve injury and regeneration: basic insights and therapeutic interventions. Curr Opin Neurol 11:557–562

    Article  PubMed  CAS  Google Scholar 

  33. Muller M, Leonhard C, Wacker K, Ringelstein EB, Okabe M, Hichey WF, Kiefer R (2003) Macrophage response to peripheral nerve injury: the quantitative contribution of resident and hematogenous macrophages. Lab Invest 83:175–185

    PubMed  Google Scholar 

  34. Nowak DA, Hermsdorfer J (2003) Selective deficits of grip force control during object manipulation in patients with reduced sensibility of the grasping digits. Neurosci Res 47:65–72

    Article  PubMed  Google Scholar 

  35. Ochi M, Wakasa M, Ikuta Y, Kwong WH (1994) Nerve regeneration in predegenerated basal lamina graft: the effect of duration of predegeneration on axonal extension. Exp Neurol 128:216–225

    Article  PubMed  CAS  Google Scholar 

  36. Rafuse VF, Milner LD, Landmesser LT (1996) Selective innervation of fast and slow muscle regions during early chick neuromuscular development. J Neurosci 16:6864–6877

    PubMed  CAS  Google Scholar 

  37. Riley DA (1978) Tenotomy delays the postnatal development of the motor innervation of the rat soleus. Brain Res 143:162–167

    Article  PubMed  CAS  Google Scholar 

  38. Robinson GA, Madison RD (2004) Motor neurons can preferentially reinnervate cutaneous pathways. Exp Neurol 190:407–413

    Article  PubMed  Google Scholar 

  39. Roganovic Z (2004) Missile-caused ulnar nerve injuries: outcomes of 128 repairs. Neurosurgery 55:1120–1129

    Article  PubMed  Google Scholar 

  40. Sulaiman OAR, Gordon T (2000) Effects of short-and long-term Schwann cell denervation on peripheral nerve regeneration, myelination and size. Glia 32:234–246

    Article  PubMed  CAS  Google Scholar 

  41. Thompson W (1983) Synapse elimination in neonatal rat muscle is sensitive to pattern of muscle use. Nature 302:614–616

    Article  PubMed  CAS  Google Scholar 

  42. Wigston DJ (1980) Transmitter release from nerve terminals undergoing suppression. Brain Res 190:175–183

    Article  PubMed  CAS  Google Scholar 

  43. Zelená J, Jirmonova I, Lierberman AR (1990) Reinnervation of transplanted pacian corpuscles by ventral root axons: ultrastructure of the regenerated nerve terminals. J Neurocytol 19:962–969

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jayme Augusto Bertelli.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bertelli, J.A., Taleb, M., Mira, J.C. et al. Functional recovery improvement is related to aberrant reinnervation trimming. A comparative study using fresh or predegenerated nerve grafts. Acta Neuropathol 111, 601–609 (2006). https://doi.org/10.1007/s00401-005-0005-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-005-0005-0

Keywords

Navigation