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Are Rat Models of Peripheral Nerve Regeneration Obsolete? A Meta-analysis of the Functional Outcomes in Rat Peripheral Nerve Injury Models
Anthony DeLeonibus, BS; Vahe Fahradyan, MD; Majid Rezaee, DDS; Frank Papay, MD; Antonio Rampazzo, MD PhD; Bahar Bassiri Gharb, MD, PhD
Cleveland Clinic Foundation
2018-02-15
Presenter: Anthony DeLeonibus
Affidavit:
This is the medical student's, Anthony DeLeonibus' original work and he was involved in all steps of this study.
Director Name: Bahar Bassiri Gharb, MD, PhD
Author Category: Medical Student
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Introduction
Rat sciatic nerve injury is the most widely utilized model in studies on peripheral nerve regeneration, however based on the assumption that nerve regeneration in rodents achieves more favorable outcomes than in humans, large animal models are increasingly favored. The purpose of this meta-analysis was to investigate if any of the available peripheral nerve regeneration models in rats could be clinically more relevant.
Methods
A PRISMA meta-analysis was performed using Pubmed, Embase, and Cochrane to assess rat sciatic function index (SFI) recovery across six scenarios: 1) intact sciatic nerve, 2) transection without repair, 3) transection with repair, 4) isogenic grafts, 5) allogenic grafts with tacrolimus treatment, and 6) hindlimb transplantation. Parameters included surgical model, number of rats, SFI, nerve graft size, and follow-up time.
Results
A hundred and twenty-five papers satisfied the initial inclusion criteria. There was a significant difference in recovery time and degree of recovery across all surgical models (MANOVA, p<0.0005). At 20 weeks, SFI values for transections with repair were -29.72 ± 43.88 (-72.2 to -30.0), isografts were -47.31 ± 21.32 (-78.0 to -28.8), allografts with tacrolimus treatment were -61.70 ± 5.38 (-66.8 to -56.6) (one-way ANOVA F(5,108) = 28.508, p<0.0005). Isografts ≤15mm recovered significantly better than >15mm grafts (p<0.05).
Conclusion:
This study showed that nerve transection without repair and transplantation models do not achieve complete functional recovery and could therefore provide translatable information in investigational studies of different neuro-regeneration enhancing therapies.
