Evaluation of Nerve Regeneration in "Super-Healing" Mice
Scott R. Echternacht, BA1,2, Jonnby S. LaGuardia, BS2, Dalton T. LaBarge, BA2, Howard N. Langstein, MD1 and Jonathan I. Leckenby, MD, Ph.D.1, (1)University of Rochester Medical Center, Rochester, NY, (2)University of Rochester School of Medicine and Dentistry, Rochester, NY
Introduction
Twenty million Americans suffer from peripheral nerve injury, costing the United States an estimated 150 billion health-care dollars annually. Traditional approaches that seek to improve regenerative outcomes following nerve injury have largely focused on manipulating the environment or upregulating stimulatory factors to promote axonal growth. Murphy Roths Large (MRL) mice, nicknamed the "Super-healing" mice, have been extensively studied and demonstrate little or no evidence of scar formation during wound or tendon healing. The purpose of this study is to examine whether this attribute transfers to the peripheral nervous system and if the strain exhibits superior axonal regeneration.
Methods
Two strains of mice were compared: C57BL/6J and MRL/MpJ. In both groups, six-week old male mice were used (n=48). The right sciatic nerve was transected and immediately repaired using two epineural 10-0 nylon sutures. Animals were functionally assessed using walking track analysis at post-operative weeks (POW) 1, 3, 6, and 9. At each endpoint, mice were sacrificed and the sciatic nerves were harvested. Sections were analyzed using light microscopy and transmission electron microscopy to provide axonal counts distal to the neurorrhaphy.
Results
The walking track analyses were used to calculate the sciatic functional index (SFI) scores. The MRL/MpJ mice were found to have superior functional outcomes at POW 1 and 3 (p = 0.0036 and 0.0443, respectively). Although the MRL/MpJ mice had better SFI scores at POW 6 and 9, the data lacked statistical significance (p = 0.6285 and 0.2772, respectively). Surprisingly, at POW 3 and 6 the C57BL/6J mice were found to have more axons distal to the repair (p = 0.0012 and <0.001, respectively). There was no statistically significant difference in axon counts found at POW 1 and 9 (p = 0.86 and 0.81, respectively).
Conclusions
The results of this study indicate that the "Super-healing" mice recover function more expediently than the control mice. Interestingly, our data shows that they do so with fewer axons distal to the nerve repair. This may seem counterintuitive; however, we suspect that this can be explained in terms of quality versus quantity. The C57BL/6J mice sprout multiple axons in a growth cone post-injury in an effort to reinnervate the targeted muscle. We believe the MRL/MpJ mice have a more efficient regeneration process likely related to less scar formation. This study lays the foundation for future research identifying the cell lines or signaling pathways that may be responsible for this improved peripheral nerve healing.
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