title: Salmon fibrin treatment of spinal cord injury promotes functional recovery and density of serotonergic innervation.
abstract: The neural degeneration caused by spinal cord injury leaves a cavity at the injury site that greatly inhibits repair. One approach to promoting repair is to fill the cavity with a scaffold to limit further damage and encourage regrowth. Injectable materials are advantageous scaffolds because they can be placed as a liquid in the lesion site then form a solid in vivo that precisely matches the contours of the lesion. Fibrin is one type of injectable scaffold, but risk of infection from blood borne pathogens has limited its use. We investigated the potential utility of salmon fibrin as an injectable scaffold to treat spinal cord injury since it lacks mammalian infectious agents and encourages greater neuronal extension in vitro than mammalian fibrin or Matrigel®, another injectable material. Female rats received a T9 dorsal hemisection injury and were treated with either salmon or human fibrin at the time of injury while a third group served as untreated controls. Locomotor function was assessed using the BBB scale, bladder function was analyzed by measuring residual urine, and sensory responses were tested by mechanical stimulation (von Frey hairs). Histological analyses quantified the glial scar, lesion volume, and serotonergic fiber density. Rats that received salmon fibrin exhibited significantly improved recovery of both locomotor and bladder function and a greater density of serotonergic innervation caudal to the lesion site without exacerbation of pain. Rats treated with salmon fibrin also exhibited less autophagia than those treated with human fibrin, potentially pointing to amelioration of sensory dysfunction. Glial scar formation and lesion size did not differ significantly among groups. The pattern and timing of salmon fibrin's effects suggest that it acts on neuronal populations but not by stimulating long tract regeneration. Salmon fibrin clearly has properties distinct from those of mammalian fibrin and is a beneficial injectable scaffold for treatment of spinal cord injury.
authors.affiliation: Reeve-Irvine Research Center and Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA 92697-1705, USA.
authors.forename: Kelli G
authors.initials: KG
authors.lastname: Sharp
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Dickson
authors.forename: Steve A
authors.initials: SA
authors.lastname: Marchenko
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Yee
authors.forename: Pauline N
authors.initials: PN
authors.lastname: Emery
authors.forename: Ivo
authors.initials: I
authors.lastname: Laidmåe
authors.forename: Raivo
authors.initials: R
authors.lastname: Uibo
authors.forename: Evelyn S
authors.initials: ES
authors.lastname: Sawyer
authors.forename: Oswald
authors.initials: O
authors.lastname: Steward
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Flanagan
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D005260:Female; D005337:Fibrin / Q000008:administration & dosage / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D054457:Tissue Scaffolds
chemical_list: D005337:Fibrin