Functional and Histological Outcomes After Polyethylene Glycol Fusion of Rat Sciatic Nerve Transection.

PURPOSE: Polyethylene glycol (PEG) fusion has been reported to restore axonal continuity after nerve repair if initiated before Wallerian degeneration (WD). Sterile α and Toll/Interleukin-1 Receptor motif-containing 1 (SARM1) inhibition can potentially delay WD. We hypothesized that PEG fusion in SARM1 knockout (KO) rats would allow for improved strength and nerve regeneration following nerve transection.

METHODS

A total of 32 wild-type (WT) and 32 SARM1-KO rats underwent sciatic nerve transection, followed by standard neurorrhaphy or PEG fusion. Baseline compound nerve action potentials (CNAP) were obtained before and after transection and repair on Day 0. At 2 or 6 weeks, maximal gastrocnemius and tibialis anterior force and CNAP were measured. Analysis of variance was used to analyze effect of time and repair method on CNAP and muscle strength. Histomorphometry analysis was performed to assess axonal regeneration.

RESULTS

No difference was seen in CNAP amplitudes at any timepoint. Muscle strengths were similar at 2 weeks, but at 6 weeks, SARM1-KO PEG animals displayed significantly decreased gastrocnemius strength compared to WT suture-only and WT PEG rats (P < .01). Histomorphometry demonstrated improved axonal maintenance at 2 weeks but reduced neuronal regeneration at 6 weeks in KO animals. The PEG fusion was not shown to confer any functional or histologic advantage over standard repair, regardless of genotype.

CONCLUSIONS

The PEG fusion did not improve recovery after sciatic nerve transection and repair compared to suture alone. The SARM1-KO rats demonstrated a greater number of myelinated axons at 2 weeks after repair compared to WT rats, suggesting delayed WD, but this was not maintained at 6 weeks. Regardless of repair technique, WT animals had improved gastrocnemius muscle recovery at 6 weeks compared to SARM1-KO animals.

CLINICAL RELEVANCE: The PEG fusion does not appear to provide additional benefit over standard nerve repair. Although SARM1 inhibition may delay initial WD, complete knockout may result in delayed functional recovery.