A Rabbit Model for Peripheral Nerve Reconstruction Studies Avoiding Automutilation Behavior

Abstract

Background The rabbit sciatic nerve injury model may represent a valuable alternative for critical gap distance seen in humans but often leads to automutilation. In this study, we modified the complete sciatic nerve injury model for avoiding autophagy. Materials and Methods In 20 adult female New Zealand White rabbits, instead of transecting the complete sciatic nerve, we unilaterally transected the tibial portion and preserved the peroneal portion. Thereby loss of sensation in the dorsal aspect of the paw was avoided. The tibial portion was repaired in a reversed autograft approach in a length of 2.6 cm. In an alternative repair approach, a gap of 2.6 cm in length was repaired with a chitosan-based nerve guide. Results During the 6-month follow-up period, there were no incidents of autotomy. Nerve regeneration of the tibial portion of the sciatic nerve was evaluated histologically and morphometrically. A clear difference between the distal segments of the healthy contralateral and the repaired tibial portion of the sciatic nerve was detectable, validating the model. Conclusion By transecting the isolated tibial portion of the rabbit sciatic nerve and leaving the peroneal portion intact, it was possible to eliminate automutilation behavior.

Keywords: automutilation behavior; peripheral nerve reconstruction; rabbit model.

Fig. 1

Anatomy of the rabbit sciatic nerve. The sciatic nerve divides into its main branches the peroneal nerve and the tibial nerve. The tibial nerve is the largest branch and gives rise to the sural nerve branch at midthigh level.

Fig. 2

Reconstruction of the tibial portion of the sciatic nerve. The proximal and distal ends of the nerve were either reconstructed with autologous nerve graft (ANG), ( A ) or fixed by 10–0 epineurial sutures each with a 2-mm overlap inside 3-cm chitosan tube ( B ), creating a 2.6-cm gap between the two ends and microsurgically reconnected.

Fig. 3

Representative pictures of toluidine blue-stained semi-thin cross-sections of distal nerve segments 6 months after reconstruction surgery. Images show healthy nerve segments ( A, C, E ) serving as control compared with distal nerve segments of sciatic nerves, which were reconstructed with autologous nerve grafts (ANGs) ( B, D, F ). Healthy nerve samples reveal axons with large diameters and thick myelin sheaths. Pictures of distal nerve segments of autologous nerve graft reconstructed sciatic nerves show successfully regenerated smaller axons with thinner myelin sheaths as well as axonal degeneration (indicated by arrow). Black scale bars display 10 µm.

Fig. 4

Scatter plot with bar graphs displaying results from histomorphometrical analyses of distal nerve segments from healthy or autologous nerve graft reconstructed sciatic nerves at 6 months of postsurgery. Cross-sectional areas ( A ), nerve fiber densities ( B ), and total numbers of myelinated fibers ( C ) are shown. No significant differences ( p  < 0.05) were detected by Mann–Whitney test. Results are presented as mean ± SEM (healthy nerve: n  = 10; ANG: n  = 3). ANG, autologous nerve graft; SEM, standard error of mean.

Fig. 5

Scatter plot with bar graphs displaying results from histomorphometrical analyses of distal nerve segments from healthy or autologous nerve graft reconstructed sciatic nerves at 6 months post-surgery. Axon diameters ( A ), fiber diameters ( B ), g -ratios ( C ), and myelin thicknesses ( D ) are shown. Significant differences ( p  < 0.05) were detected by Mann–Whitney test (** p  < 0.01 vs. healthy nerve). Results are presented as mean ± SEM (healthy nerve: n  = 10; ANG: n  = 3). ANG, autologous nerve graft; SEM, standard error of mean.