Identifying the long-term role of inducible nitric oxide synthase after contusive spinal cord injury using a transgenic mouse model

Dominic M. Maggio, Amanpreet Singh, J. Bryan Iorgulescu, Drew H. Bleicher, Mousumi Ghosh, Michael M. Lopez, Luis M. Tuesta, Govinder Flora, W. Dalton Dietrich, Damien D. Pearse

Research output: Contribution to journalArticle

2 Scopus citations

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 using inos-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.

Original languageEnglish (US)
Article number245
JournalInternational journal of molecular sciences
Volume18
Issue number2
DOIs
StatePublished - Feb 2017

Keywords

  • Angiogenesis
  • Axon
  • Function
  • Inducible nitric oxide synthase
  • Knockout
  • Neuroprotection
  • Oxidative stress

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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