Immunomodulatory effect of the purine nucleoside inosine following spinal cord contusion injury in rat

Spinal Cord. 2008 Jan;46(1):39-44. doi: 10.1038/sj.sc.3102057. Epub 2007 Apr 3.

Abstract

Study design: In vivo study using a moderate spinal cord contusion injury (SCI) model in adult rat.

Objective: To assess the immunomodulatory effects of the purine nucleoside inosine on macrophage/microglia activation at and near the lesion site and in white matter areas remote from the injury epicenter.

Setting: Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY, USA.

Methods: Animals (N=56) were injured using a moderate SCI at T9-T10 spinal level and were divided into three groups, depending on treatment paradigm. Rats received either intraperitoneal or subcutaneous injections of inosine (N=28) or vehicle (N=28). Spinal cord tissue was processed for ED-1 immunoreactivity and the volume fraction of ED-1(+) profiles was calculated using the Cavalieri method and unbiased stereology.

Results: The volume fraction of ED-1(+) profiles within gray and lateral white matter regions at and around the lesion site was significantly reduced only following a twice daily-6 week treatment course, compared with vehicle controls, and white matter areas remote from the lesion were unaffected by all inosine treatment paradigms.

Conclusions: Continued subcutaneous delivery of inosine, beginning 15-min post-SCI and persisting throughout the survival period of 6 weeks exerted immunomodulatory effects at and around the lesion site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Biomarkers / metabolism
  • Chemotaxis, Leukocyte / drug effects
  • Chemotaxis, Leukocyte / immunology
  • Disease Models, Animal
  • Female
  • Gliosis / drug therapy
  • Gliosis / immunology
  • Gliosis / prevention & control
  • Immunologic Factors / immunology
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / therapeutic use
  • Injections, Intraperitoneal
  • Injections, Subcutaneous
  • Inosine / immunology
  • Inosine / pharmacology*
  • Inosine / therapeutic use
  • Macrophages / drug effects
  • Macrophages / immunology
  • Microglia / drug effects
  • Microglia / immunology
  • Purine Nucleosides / immunology
  • Purine Nucleosides / pharmacology
  • Purine Nucleosides / therapeutic use
  • Rats
  • Rats, Long-Evans
  • Spinal Cord / drug effects*
  • Spinal Cord / immunology*
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / immunology*
  • Spinal Cord Injuries / physiopathology
  • Treatment Outcome

Substances

  • Biomarkers
  • Immunologic Factors
  • Purine Nucleosides
  • Inosine