title: Identifying the Long-Term Role of Inducible Nitric Oxide Synthase after Contusive Spinal Cord Injury Using a Transgenic Mouse Model.
abstract: Inducible nitric oxide synthase (iNOS) is a potent mediator of oxidative stress during neuroinflammation triggered by neurotrauma or neurodegeneration. We previously demonstrated that acute iNOS inhibition attenuated iNOS levels and promoted neuroprotection and functional recovery after spinal cord injury (SCI). The present study investigated the effects of chronic iNOS ablation after SCI usinginos-null mice.iNOS-/-knockout and wild-type (WT) control mice underwent a moderate thoracic (T8) contusive SCI. Locomotor function was assessed weekly, using the Basso Mouse Scale (BMS), and at the endpoint (six weeks), by footprint analysis. At the endpoint, the volume of preserved white and gray matter, as well as the number of dorsal column axons and perilesional blood vessels rostral to the injury, were quantified. At weeks two and three after SCI,iNOS-/-mice exhibited a significant locomotor improvement compared to WT controls, although a sustained improvement was not observed during later weeks. At the endpoint,iNOS-/-mice showed significantly less preserved white and gray matter, as well as fewer dorsal column axons and perilesional blood vessels, compared to WT controls. While short-term antagonism of iNOS provides histological and functional benefits, its long-term ablation after SCI may be deleterious, blocking protective or reparative processes important for angiogenesis and tissue preservation.
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. dominic.maggio@nih.gov.|Department of Neurological Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. dominic.maggio@nih.gov.|Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institute of Heath, Bethesda, MD 20824, USA. dominic.maggio@nih.gov.
authors.forename: Dominic M
authors.initials: DM
authors.lastname: Maggio
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. amanpu@gmail.com.
authors.forename: Amanpreet
authors.initials: A
authors.lastname: Singh
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. jbi2001@med.cornell.edu.|Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. jbi2001@med.cornell.edu.
authors.forename: J Bryan
authors.initials: JB
authors.lastname: Iorgulescu
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. drew.bleicher@jhsmiami.org.
authors.forename: Drew H
authors.initials: DH
authors.lastname: Bleicher
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. mghosh@med.miami.edu.|Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA. mghosh@med.miami.edu.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Ghosh
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Michael.Lopez@mch.com.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lopez
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. luis_tuesta@hms.harvard.edu.|Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. luis_tuesta@hms.harvard.edu.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Tuesta
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. gjsflora@gmail.com.
authors.forename: Govinder
authors.initials: G
authors.lastname: Flora
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. ddietrich@miami.edu.|Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA. ddietrich@miami.edu.|The Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA. ddietrich@miami.edu.|The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA. ddietrich@miami.edu.|Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. ddietrich@miami.edu.|Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL 33136, USA. ddietrich@miami.edu.
authors.forename: W Dalton
authors.initials: WD
authors.lastname: Dietrich
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA. DPearse@med.miami.edu.|Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USA. DPearse@med.miami.edu.|The Neuroscience Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA. DPearse@med.miami.edu.|The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA. DPearse@med.miami.edu.|Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL 33136, USA. DPearse@med.miami.edu.
authors.forename: Damien D
authors.initials: DD
authors.lastname: Pearse
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D066128:Gray Matter / Q000378:metabolism; D007382:Intermediate Filaments / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D020671:Posterior Horn Cells / Q000378:metabolism; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000534:rehabilitation; D066127:White Matter / Q000378:metabolism
chemical_list: D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II
keywords: angiogenesis; axon; function; inducible nitric oxide synthase; knockout; neuroprotection; oxidative stress