Effect of conduit repair on aberrant motor axon growth within the nerve graft in rats

Abstract

After peripheral nerve injury, minimizing axonal misdirection has been a matter of importance to obtain good functional outcomes. In general, it becomes more challenging as the nerve defect length is longer. As previous works suggested that a conduit repair leaving a short gap could induce some target-specific reinnervation, we expected that a distally placed conduit combined with nerve graft would enhance the specificity of reinnervation, especially in dealing with a long gap. To test this, a 14-mm-long gap was created in the rat sciatic nerves and repaired with either 1) whole nerve graft (WG), 2) interfascicular nerve grafts (FG), or 3) whole nerve graft combined with distally placed silicone tube leaving a 5-mm gap (TUBG). At the end of follow up, the extent of target specific reinnervation (measurement of the compound muscle action potentials evoked by stimulation of the sciatic nerve and its tibial and common peroneal fascicles) and the accuracy of motoneuronal projection (sequential retrograde labeling of the common peroneal motor pool) were assessed. Both assessments revealed that groups FG and TUBG had a similar selectivity, which was significantly higher than in group WG. Consistent with these results, the functional recovery as assessed by walking track analysis showed no significant difference between groups FG and TUBG, whereas those were significantly superior to group WG. In contrast, histomorphometric assessment of the regenerating axons and wet muscle weight showed no significant difference among the three groups. In conclusion, conduit repair would have some effects on reducing motor axonal misdirection, and it might be more effective when used in the management of a large defect in combination with nerve graft.

Correlation of three sciatic functional indices with histomorphometric findings in a rat sciatic nerve allograft repair model

“…However, due to the aforementioned possibility of ''fiber mismatch'' and poly-innervation of motor endplates, 39,40,41 35 reported an increase of the SFI from 2100 to 233 at 15 weeks after sciatic nerve reconstruction with a nerve guide bridging a gap of 1 cm, which failed to meet normal levels and was comparable to data for SFI 1 in this study. Our results for the SFI 1 of experimental group II show a twophase course reported also in other studies for SFI 3 , 35,56 reaching the plateau at 12 weeks p.o., but a two-phase course was neither observed for SFI 2 nor for SFI 3 in this study.…”

“…In contrast to a crush model, in a graft model, total functional recovery is unlikely because of the phenomenon of fiber mismatching. [39][40][41] To achieve at least partial nerve recovery, FK 506 was admitted in a low-dosage (0.1 mg/kg/day), which was sufficient for minor immunosuppression 23,34 and permitted on the one hand to induce rejection to eliminate allogenic Schwann cells during the first weeks after grafting, but on the other hand to preserve the architecture of the graft. The loss of Schwann cells renders a graft acellular, providing a poor, albeit permissive, environment for nerve regeneration.…”

Functional recovery after implantation of artificial nerve grafts in the rat- a systematic review

“…The fact that functional performance was better for experimental groups with lower nerve fibre density is also seen in other studies. The group of Tomita [17] could show higher fibre density in all experimental groups undergoing surgery (whole nerve graft, fascicular nerve graft and whole nerve graft and silicone tube) compared to the control group undergoing no surgery and serving as the gold standard for functional performance. Also in the two above mentioned studies from Evans form 2000 and 2002, functional outcome is better for the experimental groups showing low fibre density than in the groups with high fibre density [9,13].…”

“…For electrophysiological tests, the respective studies utilized either compound muscle action potential (CMAP) or nerve conduction velocity. Tomita [17] found highest CMAP for their control group undergoing no surgery. They additionally found almost equal CMAP (68,1% and 73,2%) of the sciatic nerve 12 weeks after surgery in the functionally equal study groups (fascicular nerve graft, nerve graft and silicone tube, SFI -50 in both cases).…”

“…Several of the studies used weight analysis of a muscle innervated by the operated nerve as a parameter for regen-eration, such as the studies of Tomita, our group and Evans [6,9,13,17]. Results however are mostly contradictory.…”