Inhibition of Wallerian Degeneration Leads to Decreased Functional Recovery 6 Weeks After Delayed Repair of Transected Rat Sciatic Nerve

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Background: Sterile Alpha and TIR Motif Containing 1 (SARM1) is the central executioner of Wallerian degeneration (WD) following axonal injury, with its inhibition having been shown to delay WD. However, little is known about its effect on functional recovery after nerve transection and repair. This study aimed to evaluate whether recovery after nerve transection and delayed repair is enhanced in an SARM1 knockout (KO) model. Methods: A total of 16 SARM1 KO and 16 wild-type (WT) Lewis rats underwent sciatic nerve transection, followed by repair at 4 days with functional analysis at either 2 or 6 weeks. Primary outcome measures included muscle tetanic force, compound nerve action potential (CNAP) amplitude and latency, and sciatic function index (SFI). Both SARM1 KO and WT groups were compared using independent t tests with a priori level of significance of P ≤ .05. Results: The SARM1 KO rats displayed significantly lower tibialis anterior (1.43 ± 0.98 N vs 2.56 ± 1.43 N, P = .016) and gastrocnemius (2.35 ± 0.64 N vs 4.48 ± 1.32 N, P = .002) muscle strength at 6 weeks. There were no differences in CNAP amplitudes or latencies at 2 or 6 weeks after delayed repair compared with WT. There was no difference in SFI between SARM1 KO and WT groups at 2 or 6 weeks after repair. Conclusions: The SARM1 KO impeded recovery of muscle strength after nerve transection and delayed repair. Knockout rodents also appeared to have increased scarring, reflective of poor axonal regeneration. Further work should aim to better understand the inhibitory effects of SARM1 deletion and its role in nerve regeneration.

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