Polyethylene Glycol Fusion Does Not Improve Medium Term Functional Outcomes After Rat Sciatic Nerve Transection & Repair
David M Brogan, MD, MSc1; Tony Y Lee, BA2; Mark Feger, MD, PhD2; Jesse Hu, MD3; Christopher J Dy, MD2
1Washington University School of Medicine, St. Louis, MO; 2Washington University in St. Louis, St. Louis, MO; 3Washington University School of Medicine, Saint Louis, MO
Introduction: Polyethylene glycol (PEG) fusion has demonstrated improved axonal continuity after nerve repair while sterile alpha and Toll/interleukin-1 receptor motif-containing 1 (SARM-1) inhibition prevents Wallerian degeneration. We therefore hypothesized that PEG fusion would improve medium term muscle recovery after rat sciatic nerve transection and repair in wild type and SARM-1 knockout (KO) models.
Materials & Methods: 32 wild-type (WT) and 32 SARM-1 KO rats from our institutional colony were divided into 4 groups each (See Table 1) according to genotype, repair method, and non-survival testing timeframe. Baseline compound nerve action potential (CNAP) recordings were obtained before and after nerve transection and repair on Day 0. Maximal isometric tetanic force measurements of gastrocnemius and tibialis anterior muscles were performed at non-survival surgery, along with CNAP recordings. Strength of each injured muscle was normalized against the uninjured side. Two way ANOVA testing was used to analyze effect of time and repair method on CNAP latency and amplitude. One way ANOVA was used to assess effect of repair method on muscle strength. Post-hoc Tukey’s multiple comparison test was used for between group comparisons.
Results: No difference was seen in CNAP amplitudes between groups at any time point, although all groups demonstrated robust CNAP amplitudes immediately after repair. At 2 weeks, no significant difference was found between PEG fusion vs suture alone in tibialis anterior (p=0.59) or gastrocnemius strength (p=0.50) independent of genotype. At 6 weeks, a difference in gastrocnemius muscle strength was noted between groups (p<0.01), with worse recovery in the SARM KO PEG group compared to WT suture (p <0.01) and WT PEG (p=0.03). No difference was seen between the repair methods in WT or SARM1 KO animals (Figure 1).
Conclusion:
- CNAP recordings are present immediately after repair with and without the use of PEG fusion.
- PEG fusion does not improve muscle strength at 2 weeks or 6 weeks after nerve repair compared to suture alone in WT animals.
- SARM-1 KO animals demonstrated weaker gastrocnemius muscle force at 6 weeks compared to WT animals.
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