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PEG-fused Allografts Produce Rapid Behavioral Recovery AfterSegmental Nerve Loss
David Colton Riley, BS1; Kevin Sexton, MD1; G. D. Bittner, PhD2; Cameron Ghergherehchi, BS2; Bruce Shack, MD1; W. P. Thayer, MD, PhD1
1Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN; 2Department of Neurobiology, University of Texas at Austin, Austin, TX
Introduction: Every year in the United States approximately 360,000 people suffer from peripheral nerve injuries and roughly 12% of operations performed for traumatic neuropathy involve patients with segmental nerve loss. Of these operations less than 50% show meaningful recovery. Presently, the most dependable method of repair for such major deficiencies is autologous nerve grafts. Substitutes to nerve autografting are being pursued due to donor site morbidity and limited functional recovery. Polyethylene Glycol (PEG) has demonstrated an ability to improve behavioral outcome after nerve transection as well as nerve autografting. We hypothesized that the previously established PEG therapy could improve functional outcome after nerve allografting.
Materials and Methods: In this experiment we used a segmental rat sciatic nerve injury model in which we restored a 0.8-1.0 cm gap with a 1.0 cm nerve segment from a separate rat (allograft) using microsurgical techniques. The experimental animals were treated with a combination of solutions including Plasmalyte A (calcium free saline), Methylene Blue, Polyethylene Glycol (PEG), and Lactated Ringers (calcium containing saline); control animals received all solutions except for PEG. Animals underwent weekly (1w-6w) behavioral assessments using the Sciatic Functional Index. At 6 weeks post-op animals were perfused and fixed for thick cross sections.
Results: Following removal of 0.8-1cm segments of rat sciatic nerves, we report that micro-sutured allografts treated with polyethylene glycol (PEG) rapidly and permanently restore axonal continuity within minutes as assessed by action potential conduction (p<0.001) and intracellular diffusion of dye (Fig 1). Behavioral functions are largely restored (80%) within 2-4 weeks as measured by the sciatic functional index (SFI) in PEG treated animals and are associated with increased number of axons in PEG-fused allografts (p<0.001).
Conclusions: Our data suggests that use of microsutures, allografts, and PEG-fusion procedures might produce a paradigm shift in the clinical treatment of traumatic injuries to peripheral nerves for which the current gold-standard for simple cuts is micro-suture of the severed ends.
Figure 1 – Control nerve (left) and PEG-fused nerve (right) loaded proximally with fluorescent intra-axonal dye (Texas-Red) immediately following in-vivo repair. White arrows indicate proximal site of nerve severance.
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