Early peripheral nerve regeneration after crushing, sectioning, and freeze studied by implanted electrodes in the cat

Abstract

Regeneration of axons after Wallerian degeneration is influenced by various factors localized to the distal nerve stump. We have examined elongation of axons to assess the relative influence of basal lamina and of Schwann cells in lesions with and without interruption of the Schwann cell tubes. In particular, we wanted to follow the growth of axons throughout the same distal nerve stump. Silicone cuff and patch electrodes with multiple contacts were therefore implanted around hindlimb nerves proximal and distal to the lesion. The tibial nerve was cut and sutured (15 nerves) or crushed (10 nerves). A 20-25-mm-long segment distal to the lesion was in addition frozen in four crushed and in seven sectioned nerves to eliminate the Schwann cells. Six unlesioned tibial nerves from four cats served as control. Reinnervation of plantar muscle occurred 42-54 d after nerve crushing and 42- 84 d after nerve sectioning (P < 0.01). Regeneration was followed by weekly electrophysiological observations that allowed serial identification of the fastest-growing individual axons, with conduction velocities of 0.5-3 m/sec and amplitudes of 0.15-0.5 μV. Unmyelinated axons were present at the most distal lead of the electrode array from which action potentials were identified. The rate of elongation after both crushing and crush+freeze was 3-4 mm/d, and after sectioning only 2.5 mm/d (P < 0.01). Freezing in addition to sectioning was associated with even slower elongation of 1.2 mm/d. Distal to the frozen portion of the nerve elongation accelerated. Our findings suggest that regeneration was slowed throughout the nerve distal to a sectioning compared with a crushing lesion, and that depletion of Schwann cells only influenced axonal elongation after interruption of the basal lamina. This suggests that the basal lamina tubes at the lesion site may facilitate the action of neurotropic factors of distal origin.