title: A Novel Rodent Orthotopic Forelimb Transplantation Model That Allows for Reliable Assessment of Functional Recovery Resulting From Nerve Regeneration.
abstract: Improved nerve regeneration and functional outcomes would greatly enhance the utility of vascularized composite allotransplantation (VCA) such as hand and upper extremity transplantation. However, research aimed at achieving this goal has been limited by the lack of a functional VCA animal model. We have developed a novel rat midhumeral forelimb transplant model that allows for the characterization of upper extremity functional recovery following transplantation. At the final end point of 12 weeks, we found that animals with forelimb transplantation including median, ulnar and radial nerve coaptation demonstrated significantly improved grip strength and forelimb function as compared to forelimb transplantation without nerve approximation (grip strength: 1.71N ± 0.57 vs. no appreciable recovery; IBB scale: 2.6 ± 0.7? vs. 0.8 ± 0.40; p = 0.0005), and similar recovery to nerve transection-and-repair only (grip strength: 1.71N ± 0.57 vs. 2.03 ± 0.42.6; IBB scale: 2.6 ± 0.7 vs. 2.8 ± 0.8; p = ns). Moreover, all forelimb transplant animals with nerve coaptation displayed robust axonal regeneration with myelination and reduced flexor muscle atrophy when compared to forelimb transplant animals without nerve coaptation. In conclusion, this is the first VCA small-animal model that allows for reliable and reproducible measurement of behavioral functional recovery in addition to histologic evaluation of nerve regeneration and graft reinnervation.
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.|Department of Visceral, Transplant, and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors: B
authors: B
authors: Kern
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: J D
authors: JD
authors: Budihardjo
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: S
authors: S
authors: Mermulla
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: A
authors: A
authors: Quan
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: C
authors: C
authors: Cadmi
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: J
authors: J
authors: Lopez
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: M
authors: M
authors: Khusheim
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: S
authors: S
authors: Xiang
authors: Department of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: J
authors: J
authors: Park
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: G J
authors: GJ
authors: Furtmüller
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: K A
authors: KA
authors: Sarhane
authors: Department of Visceral, Transplant, and Thoracic Surgery, Innsbruck Medical University, Innsbruck, Austria.
authors: S
authors: S
authors: Schneeberger
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: W P A
authors: WP
authors: Lee
authors: Department of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: A
authors: A
authors: Hoke
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: S H
authors: SH
authors: Tuffaha
authors: Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.
authors: G
authors: G
authors: Brandacher
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005552:Forelimb / Q000601:surgery*; D008297:Male; D009416:Nerve Regeneration / Q000502:physiology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D063986:Vascularized Composite Allotransplantation
keywords: animal models: murine; basic (laboratory) research/science; diagnostic techniques and imaging; neurology; rehabilitation; translational research/science; vascularized composite and reconstructive transplantation