2553: Measuring functional recovery after chronic denervation of peripheral nerves: A novel rat forelimb model

2553: Measuring functional recovery after chronic denervation of peripheral nerves: A novel rat forelimb model Amy Quan, Joseph Lopez, Joshua Budihardjo, Sara Mermulla, Tariq Jawadi, Howard Wang, Ahmet Hoke, Sami Tuffaha, W. P. Andrew Lee, and Gerald Brandacher Johns Hopkins University School of Medicine, Vascularized Composite Allotransplantation (VCA) Laboratory, Baltimore, MD, USA Background Functional outcomes after vascularized composite allotransplantation (VCA) depend on nerve regeneration. After transplantation, the recipient peripheral nerve axons slowly grow and reinnervate the graft. Meanwhile, the target composite tissues (i.e., muscle, nerves) are chronically denervated, causing significant damage to axons, Schwann cells, and muscle, which leads to decreased nerve regeneration potential. There are currently no studies that reliably measure the effects of chronic denervation (CD) on graft function. Thus, we have developed a novel nerve injury rat model that optimizes the measurement of functional recovery after CD. Methods In our forelimb chronic denervation model, the median nerve was transected at the mid-humerus level and left in discontinuity for 0, 8, or 12 weeks. After the period of CD, the distal median nerve stump was coapted to the proximal end of a freshly axotomized ulnar nerve. Group 1 rats underwent 8 weeks of CD (n D 8); Group 2 underwent 12 weeks of CD (n D 8); Group 3 (positive control) did not undergo CD but instead underwent immediate ulnar-median neurorrhaphy (n D 8); and Group 4 (naive control) did not undergo any surgery (nD 8). Functional recovery was monitored weekly by measuring grip strength, feeding ability, and compound muscle action potentials (CMAPs) in median nerve-innervated muscles. Animals were sacrificed at 14 weeks after ulnar-median neurorrhaphy for assessment of axonal regeneration and degree of muscle atrophy.