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

Mohammed Barham; Jonas Andermahr; Henryk Majczyński; Urszula Sławińska; Johannes Vogt; Wolfram F Neiss

doi:10.3389/fneur.2022.1050822

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

Front Neurol. 2023 Jan 19:13:1050822. doi: 10.3389/fneur.2022.1050822. eCollection 2022.

Authors

Mohammed Barham¹, Jonas Andermahr², Henryk Majczyński³, Urszula Sławińska³, Johannes Vogt^{1

4}, Wolfram F Neiss⁵

Affiliations

¹ Department II of Anatomy, University of Cologne and University Hospital of Cologne, Cologne, Germany.
² Kreiskrankenhaus Mechernich, Mechernich, Germany.
³ Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa, Poland.
⁴ Cluster of Excellence for Aging Research (CECAD) and Center of Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
⁵ Department I of Anatomy, University of Cologne and University Hospital of Cologne, Cologne, Germany.

Abstract

Background and purpose: After peripheral nerve lesions, surgical reconstruction facilitates axonal regeneration and motor reinnervation. However, functional recovery is impaired by aberrant reinnervation.

Materials and methods: We tested whether training therapy by treadmill exercise (9 × 250 m/week) before (run-idle), after (idle-run), or both before and after (run-run) sciatic nerve graft improves the accuracy of reinnervation in rats. Female Lewis rats (LEW/SsNHsd) were either trained for 12 weeks (run) or not trained (kept under control conditions, idle). The right sciatic nerves were then excised and reconstructed with 5 mm of a congenic allograft. One week later, training started in the run-run and idle-run groups for another 12 weeks. No further training was conducted in the run-idle and idle-idle groups. Reinnervation was measured using the following parameters: counting of retrogradely labeled motoneurons, walking track analysis, and compound muscle action potential (CMAP) recordings.

Results: In intact rats, the common fibular (peroneal) and the soleus nerve received axons from 549 ± 83 motoneurons. In the run-idle group, 94% of these motoneurons had regenerated 13 weeks after the nerve graft. In the idle-run group, 81% of the normal number of motoneurons had regenerated into the denervated musculature and 87% in both run-run and idle-idle groups. Despite reinnervation, functional outcome was poor: walking tracks indicated no functional improvement of motion in any group. However, in the operated hindlimb of run-idle rats, the CMAP of the soleus muscle reached 11.9 mV (normal 16.3 mV), yet only 6.3-8.1 mV in the other groups.

Conclusion: Treadmill training neither altered the accuracy of reinnervation nor the functional recovery, and pre-operative training (run-idle) led to a higher motor unit activation after regeneration.

Keywords: misdirected reinnervation; motoneuron; nerve regeneration; physical exercise; recovery of function; sciatic nerve.

Grants and funding

This work was supported by the European Union COST Action B30: Neural Regeneration and Plasticity. This study was supported by the CRC 1451 to JV and MB and Cluster of Excellence for Aging Research (CECAD), University of Cologne, 50931 Cologne, Germany.