Functional and structural effects of GM-1 ganglioside treatment on peripheral nerve grafting in the rat

Peripheral nerve regeneration after traumatic injury and standard repair with a nerve autograft is usually incomplete. This study tested the influence of graft vascularity and pharmacological intervention with GM-1 ganglioside on nerve regeneration in a rat sciatic nerve model. Controls included an unoperated contralateral side and sham-operated groups either with or without the GM-1. During the 5 months of recovery, locomotion was tested by the sciatic function index (SFI). At killing, anesthetized animals were prepared for nerve conduction velocity (NCV) studies, followed by the wet weight of the gastrocnemius muscle (expression of atrophy), toe-chewing (expression of lesion severity and sensory loss), and histological examination of the nerve segments. The SFI showed a slight but significant recovery for both the vascular and avascular groups (34% at 20 weeks), but when GM-1 ganglioside treatment was included, the SFI was poor throughout (20-33%). The average NCV of the graft groups without GM-1 was 46% to 57% of the normal nerve (52.7 m/s), whereas for the groups treated with GM-1, it was 63% to 64% of normal; treatment of the non-vascular graft group significantly improved recovery. A uniformly poor recovery from muscle atrophy was seen for all nerve graft groups (62-67%) compared with normal controls. The mean number of toes per foot chewed was 1.9 and 2.4 in graft groups without GM-1 treatment and 0.9 and 1.3 in graft groups treated with GM-1. This treatment significantly reduced both the extent and the number of animals exhibiting autotomy. The qualitative microscopic appearance of the distal nerve segment in all surgical groups was similar. We conclude that the systemic addition of GM-1 ganglioside enhances only some aspects of regeneration in grafted nerves, possibly with a preferential effect on sensory nerve regeneration and functional recovery.