title: Polyethylene glycol-fused allografts produce rapid behavioral recovery after ablation of sciatic nerve segments.
abstract: Restoration of neuronal functions by outgrowths regenerating at ∼1 mm/day from the proximal stumps of severed peripheral nerves takes many weeks or months, if it occurs at all, especially after ablation of nerve segments. Distal segments of severed axons typically degenerate in 1-3 days. This study shows that Wallerian degeneration can be prevented or retarded, and lost behavioral function can be restored, following ablation of 0.5-1-cm segments of rat sciatic nerves in host animals. This is achieved by using 0.8-1.1-cm microsutured donor allografts treated with bioengineered solutions varying in ionic and polyethylene glycol (PEG) concentrations (modified PEG-fusion procedure), being careful not to stretch any portion of donor or host sciatic nerves. The data show that PEG fusion permanently restores axonal continuity within minutes, as initially assessed by action potential conduction and intracellular diffusion of dye. Behavioral functions mediated by the sciatic nerve are largely restored within 2-4 weeks, as measured by the sciatic functional index. Increased restoration of sciatic behavioral functions after ablating 0.5-1-cm segments is associated with greater numbers of viable myelinated axons within and distal to PEG-fused allografts. Many such viable myelinated axons are almost certainly spared from Wallerian degeneration by PEG fusion. PEG fusion of donor allografts may produce a paradigm shift in the treatment of peripheral nerve injuries.
authors.affiliation: Department of Plastic Surgery, Vanderbilt School of Medicine, Nashville, Tennessee; Department of Neuroscience, University of Texas at Austin, Austin, Texas.
authors.forename: D C
authors.initials: DC
authors.lastname: Riley
authors.forename: G D
authors.initials: GD
authors.lastname: Bittner
authors.forename: M
authors.initials: M
authors.lastname: Mikesh
authors.forename: N L
authors.initials: NL
authors.lastname: Cardwell
authors.forename: A C
authors.initials: AC
authors.lastname: Pollins
authors.forename: C L
authors.initials: CL
authors.lastname: Ghergherehchi
authors.forename: S R
authors.initials: SR
authors.lastname: Bhupanapadu Sunkesula
authors.forename: T N
authors.initials: TN
authors.lastname: Ha
authors.forename: B T D
authors.initials: BT
authors.lastname: Hall
authors.forename: A D
authors.initials: AD
authors.lastname: Poon
authors.forename: M
authors.initials: M
authors.lastname: Pyarali
authors.forename: R B
authors.initials: RB
authors.lastname: Boyer
authors.forename: A T
authors.initials: AT
authors.lastname: Mazal
authors.forename: N
authors.initials: N
authors.lastname: Munoz
authors.forename: R C
authors.initials: RC
authors.lastname: Trevino
authors.forename: T
authors.initials: T
authors.lastname: Schallert
authors.forename: W P
authors.initials: WP
authors.lastname: Thayer
mesh_terms: D000200:Action Potentials / Q000502:physiology; D064591:Allografts / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000473:pathology; D004195:Disease Models, Animal; D001523:Mental Disorders / Q000209:etiology* / Q000601:surgery*; D009043:Motor Activity; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D020426:Sciatic Neuropathy / Q000150:complications*; D013223:Statistics as Topic; D013997:Time Factors; D014184:Transplantation, Homologous / Q000379:methods*
chemical_list: D011092:Polyethylene Glycols
keywords: Wallerian degeneration; axonal regeneration; axotomy; polyethylene glycol