Functional Impact of Axonal Misdirection after Peripheral Nerve Injuries followed by Graft or Tube Repair

Abstract

Accuracy of reinnervation is one of the main factors conditioning functional recovery after brain, spinal, or peripheral axonal damage. Using the peripheral nerve as an experimental model, we studied the amount of inaccurate muscle reinnervation and its consequences on walking. Adult rats were submitted to an 8-mm resection of the sciatic nerve repaired by autograft (AG, n = 9), silicone (SIL, n = 13) or poly-L-lactate-ϵ-caprolactone (PLC, n = 11) single guides, and fascicular tubulization of peroneal and tibial branches with a dual silicone tube (FSIL, n = 9). At the end of follow-up, the sciatic nerve and its tibial and peroneal fascicles were dissected and stimulated by means of a suction electrode. In control rats, gastrocnemius and plantar muscles are fully innervated by the tibial fascicle and the tibialis anterior muscle by the peroneal nerve. None of the groups had noticeable recovery of locomotion assessed by the walking track index (SFI around -70 in all groups). After resection, all animals of groups AG, SIL, and PLC showed aberrant muscle reinnervation by axons from a non-corresponding fascicle, whereas in group FSIL only one of six regenerated animals showed misdirected activity. The proportion of inaccurate muscle activation was similar in group AG (47% for gastrocnemius, 54% for tibialis anterior, and 44% for plantar muscles) and in group SIL (42%, 42%, and 42%), and reduced in group PLC (26%, 38%, and 27%). In conclusion, fascicular silicone tubulization allowed the highest degree of accuracy but the lowest recovery, whereas resorbable PLC guides provided for the best balance between amount and accuracy of reinnervation after nerve resection.