Download PDF
J Brachial Plex Peripher Nerve Inj 2012; 07(01): e8-e14
DOI: 10.1186/1749-7221-7-5
Research article
van Neerven et al.; licensee BioMed Central Ltd.

Retrograde tracing and toe spreading after experimental autologous nerve transplantation and crush injury of the sciatic nerve: a descriptive methodological study[*]

Sabien GA van Neerven
1   Department of Plastic Surgery, Reconstructive and Hand Surgery, Burn Center, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
,
Ahmet Bozkurt
1   Department of Plastic Surgery, Reconstructive and Hand Surgery, Burn Center, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
,
Dan Mon O’Dey
1   Department of Plastic Surgery, Reconstructive and Hand Surgery, Burn Center, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
,
Juliane Scheffel
1   Department of Plastic Surgery, Reconstructive and Hand Surgery, Burn Center, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
,
Arne H Boecker
1   Department of Plastic Surgery, Reconstructive and Hand Surgery, Burn Center, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
,
Jan-Philipp Stromps
1   Department of Plastic Surgery, Reconstructive and Hand Surgery, Burn Center, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
,
Sebastian Dunda
1   Department of Plastic Surgery, Reconstructive and Hand Surgery, Burn Center, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
,
Gary A Brook
2   Institute of Neuropathology, Medical Faculty, RWTH Aachen University, Aachen, Germany
,
Norbert Pallua
1   Department of Plastic Surgery, Reconstructive and Hand Surgery, Burn Center, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
› Author Affiliations
Subject Editor:
Further Information

Publication History

30 December 2011

30 March 2012

Publication Date:
24 September 2014 (online)

   Permissions and Reprints

Abstract

Evaluation of functional and structural recovery after peripheral nerve injury is crucial to determine the therapeutic effect of a nerve repair strategy. In the present study, we examined the relationship between the structural evaluation of regeneration by means of retrograde tracing and the functional analysis of toe spreading. Two standardized rat sciatic nerve injury models were used to address this relationship. As such, animals received either a 2 cm sciatic nerve defect (neurotmesis) followed by autologous nerve transplantation (ANT animals) or a crush injury with spontaneous recovery (axonotmesis; CI animals). Functional recovery of toe spreading was observed over an observation period of 84 days. In contrast to CI animals, ANT animals did not reach pre-surgical levels of toe spreading. After the observation period, the lipophilic dye Dil was applied to label sensory and motor neurons in dorsal root ganglia (DRG; sensory neurons) and spinal cord (motor neurons), respectively. No statistical difference in motor or sensory neuron counts could be detected between ANT and CI animals.

In the present study we could indicate that there was no direct relationship between functional recovery (toe spreading) measured by SSI and the number of labelled (motor and sensory) neurons evaluated by retrograde tracing. The present findings demonstrate that a multimodal approach with a variety of independent evaluation tools is essential to understand and estimate the therapeutic benefit of a nerve repair strategy.

Keywords

Peripheral nerve injury - Repair strategy - Peripheral nerve regeneration - Neurotmesis - SSI - Sciatic nerve injury - Rat model

*This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


 

  • References

  • 1 Sunderland IR, Brenner MJ, Singham J, Rickman SR, Hunter DA, Mackinnon SE. Effect of tension on nerve regeneration in rat sciatic nerve transection model. Ann Plast Surg 2004; 53: 382-387 10.1097/01.sap.0000125502.63302.47 15385776
    CrossrefPubMedGoogle Scholar
  • 2 Seddon H. Nerve Injuries. Med Bull (Ann Arbor) 1965; 31: 4-10
    PubMedGoogle Scholar
  • 3 Sunderland S. A classification of peripheral nerve injuries producing loss of function. Brain 1951; 74: 491-516 10.1093/brain/74.4.491 14895767
    CrossrefPubMedGoogle Scholar
  • 4 Bozkurt A, Lassner F, O’Dey D, Deumens R, Bocker A, Schwendt T, Janzen C, Suschek CV, Tolba R, Kobayashi E et al: The role of microstructured and interconnected pore channels in a collagen-based nerve guide on axonal regeneration in peripheral nerves. Biomaterials 2012; 33: 1363-1375 10.1016/j.biomaterials.2011.10.069 22082619
    CrossrefPubMedGoogle Scholar
  • 5 Deumens R, Bozkurt A, Meek MF, Marcus MA, Joosten EA, Weis J, Brook GA. Repairing injured peripheral nerves: bridging the gap. Prog Neurobiol 2010; 92: 245-276 10.1016/j.pneurobio.2010.10.002 20950667
    CrossrefPubMedGoogle Scholar
  • 6 Korte N, Schenk HC, Grothe C, Tipold A, Haastert-Talini K. Evaluation of periodic electrodiagnostic measurements to monitor motor recovery after different peripheral nerve lesions in the rat. Muscle Nerve 2011; 44: 63-73 10.1002/mus.22023 21674522
    CrossrefPubMedGoogle Scholar
  • 7 Vleggeert-Lankamp CL. The role of evaluation methods in the assessment of peripheral nerve regeneration through synthetic conduits: a systematic review. Laboratory investigation. J Neurosurg 2007; 107: 1168-1189 10.3171/JNS-07/12/1168 18077955
    CrossrefPubMedGoogle Scholar
  • 8 Bervar M. Video analysis of standing–an alternative footprint analysis to assess functional loss following injury to the rat sciatic nerve. J Neurosci Methods 2000; 102: 109-116 10.1016/S0165-0270(00)00281-8 11040407
    CrossrefPubMedGoogle Scholar
  • 9 Bozkurt A, Tholl S, Wehner S, Tank J, Cortese M, O’Dey D, Deumens R, Lassner F, Schugner F, Groger A et al: Evaluation of functional nerve recovery with Visual-SSI–a novel computerized approach for the assessment of the static sciatic index (SSI). J Neurosci Methods 2008; 170: 117-122 10.1016/j.jneumeth.2008.01.006 18325596
    CrossrefPubMedGoogle Scholar
  • 10 Bain JR, Mackinnon SE, Hunter DA. Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat. Plast Reconstr Surg 1989; 83: 129-138 10.1097/00006534-198901000-00024 2909054
    CrossrefPubMedGoogle Scholar
  • 11 de Medinaceli L, Freed WJ, Wyatt RJ. An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp Neurol 1982; 77: 634-643 10.1016/0014-4886(82)90234-5 7117467
    CrossrefPubMedGoogle Scholar
  • 12 Walker JL, Evans JM, Meade P, Resig P, Sisken BF. Gait-stance duration as a measure of injury and recovery in the rat sciatic nerve model. J Neurosci Methods 1994; 52: 47-52 10.1016/0165-0270(94)90054-X 8090016
    CrossrefPubMedGoogle Scholar
  • 13 Santos PM, Williams SL, Thomas SS. Neuromuscular evaluation using rat gait analysis. J Neurosci Methods 1995; 61: 79-84 10.1016/0165-0270(95)00026-Q 8618428
    CrossrefPubMedGoogle Scholar
  • 14 Varejao AS, Cabrita AM, Geuna S, Melo-Pinto P, Filipe VM, Gramsbergen A, Meek MF. Toe out angle: a functional index for the evaluation of sciatic nerve recovery in the rat model. Exp Neurol 2003; 183: 695-699 10.1016/S0014-4886(03)00208-5 14552911
    CrossrefPubMedGoogle Scholar
  • 15 Bozkurt A, Deumens R, Scheffel J, O’Dey DM, Weis J, Joosten EA, Fuhrmann T, Brook GA, Pallua N. CatWalk gait analysis in assessment of functional recovery after sciatic nerve injury. J Neurosci Methods 2008; 173: 91-98 10.1016/j.jneumeth.2008.05.020 18577402
    CrossrefPubMedGoogle Scholar
  • 16 Zele T, Sketelj J, Bajrovic FF. Efficacy of fluorescent tracers in retrograde labeling of cutaneous afferent neurons in the rat. J Neurosci Methods 2010; 191: 208-214 10.1016/j.jneumeth.2010.06.021 20600316
    CrossrefPubMedGoogle Scholar
  • 17 Haastert K, Joswig H, Jaschke KA, Samii M, Grothe C. Nerve repair by end-to-side nerve coaptation: histologic and morphometric evaluation of axonal origin in a rat sciatic nerve model. Neurosurgery 2010; 66: 567-576 discussion 576–567 10.1227/01.NEU.0000365768.78251.8C 20173551
    CrossrefPubMedGoogle Scholar
  • 18 Luis AL, Amado S, Geuna S, Rodrigues JM, Simoes MJ, Santos JD, Fregnan F, Raimondo S, Veloso AP, Ferreira AJ et al: Long-term functional and morphological assessment of a standardized rat sciatic nerve crush injury with a non-serrated clamp. J Neurosci Methods 2007; 163: 92-104 10.1016/j.jneumeth.2007.02.017 17397932
    CrossrefPubMedGoogle Scholar
  • 19 Beer GM, Steurer J, Meyer VE. Standardizing nerve crushes with a non-serrated clamp. J Reconstr Microsurg 2001; 17: 531-534 10.1055/s-2001-17755 11598827
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Choi D, Li D, Raisman G. Fluorescent retrograde neuronal tracers that label the rat facial nucleus: a comparison of Fast Blue, Fluoro-ruby, Fluoro-emerald, Fluoro-Gold and DiI. J Neurosci Methods 2002; 117: 167-172 10.1016/S0165-0270(02)00098-5 12100982
    CrossrefPubMedGoogle Scholar
  • 21 Richmond FJ, Gladdy R, Creasy JL, Kitamura S, Smits E, Thomson DB. Efficacy of seven retrograde tracers, compared in multiple-labelling studies of feline motoneurones. J Neurosci Methods 1994; 53: 35-46 10.1016/0165-0270(94)90142-2 7527476
    CrossrefPubMedGoogle Scholar
  • 22 Decosterd I, Allchorne A, Woolf CJ. Progressive tactile hypersensitivity after a peripheral nerve crush: non-noxious mechanical stimulus-induced neuropathic pain. Pain 2002; 100: 155-162 10.1016/S0304-3959(02)00275-0 12435468
    CrossrefPubMedGoogle Scholar
  • 23 Burke D. Differences in the properties of sensory and motor axons. Rinsho Shinkeigaku 1999; 39: 97 10377822
    PubMedGoogle Scholar
  • 24 Dellon AL, Mackinnon SE. Selection of the appropriate parameter to measure neural regeneration. Ann Plast Surg 1989; 23: 197-202 10.1097/00000637-198909000-00002 2782818
    CrossrefPubMedGoogle Scholar
  • 25 Munro CA, Szalai JP, Mackinnon SE, Midha R. Lack of association between outcome measures of nerve regeneration. Muscle Nerve 1998; 21: 1095-1097 10.1002/(SICI)1097-4598(199808)21:8<1095::AID-MUS20>3.0.CO;2-S 9655134
    CrossrefPubMedGoogle Scholar
  • 26 Skouras E, Ozsoy U, Sarikcioglu L, Angelov DN. Intrinsic and therapeutic factors determining the recovery of motor function after peripheral nerve transection. Ann Anat 2011; 193: 286-303 10.1016/j.aanat.2011.02.014 21458252
    CrossrefPubMedGoogle Scholar
  • 27 Bozkurt A, Scheffel J, Brook GA, Joosten EA, Suschek CV, O’Dey DM, Pallua N, Deumens R. Aspects of static and dynamic motor function in peripheral nerve regeneration: SSI and CatWalk gait analysis. Behav Brain Res 2011; 219: 55-62 10.1016/j.bbr.2010.12.018 21168447
    CrossrefPubMedGoogle Scholar
  • 28 Kanaya F, Firrell JC, Breidenbach WC. Sciatic function index, nerve conduction tests, muscle contraction, and axon morphometry as indicators of regeneration. Plast Reconstr Surg 1996; 98: 1264-1271 discussion 1272–1264 10.1097/00006534-199612000-00023 8942915
    CrossrefPubMedGoogle Scholar
  • 29 de Medinaceli L. Interpreting nerve morphometry data after experimental traumatic lesions. J Neurosci Methods 1995; 58: 29-37 10.1016/0165-0270(94)00156-B 7475231
    CrossrefPubMedGoogle Scholar
  • 30 Tomov TL, Guntinas-Lichius O, Grosheva M, Streppel M, Schraermeyer U, Neiss WF, Angelov DN. An example of neural plasticity evoked by putative behavioral demand and early use of vibrissal hairs after facial nerve transection. Exp Neurol 2002; 178: 207-218 10.1006/exnr.2002.8040 12504880
    CrossrefPubMedGoogle Scholar