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

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. © 2008 International Spinal Cord Society All rights reserved.