Citation

Bao F, Omana V, Brown A, Weaver L. J. Neurotrauma 2011; 29(8): 1626-1637.

Affiliation

Robarts Research Institute, Spinal Cord Injury Team, London, Ontario, Canada; fbao@robarts.ca.

Copyright

(Copyright © 2011, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2011.2190

PMID

22150233

Abstract

The systemic inflammatory response syndrome (SIRS) follows spinal cord injury (SCI) and causes damage to the lungs, kidney and liver due to an influx of inflammatory cells from the circulation. After SCI in rats, the SIRS develops within 12 h and is sustained for at least 3 days. We have previously shown that blockade of the CD11d/CD18 integrin reduces inflammation-driven secondary damage to the spinal cord. This treatment reduces the SIRS after SCI (Bao, et al, Exp. Neurol., 2011b). In another study we found that blockade of the ą4ß1 integrin limited secondary cord damage more effectively than blockade of CD11d/CD18. Therefore, we considered it important to assess effects of an anti-α4ß1 treatment on the SIRS in the lung, kidney and liver after SCI. An anti-α4 antibody was given iv at 2 h after SCI at the 4th thoracic segment and effects on the organs were evaluated at 24 h after injury. The migration of neutrophils into the lungs and liver was markedly reduced and all three organs contained fewer macrophages. In the lungs and liver, activation of oxidative enzymes MPO, iNOS, COX-2 and gp91phox, production of free radicals, lipid peroxidation, and cell death, were substantially and similarly reduced. Treatment effects were less robust in the kidney. Overall, the efficacy of the anti-ą4ß1 treatment did not differ greatly from that of the anti-CD11d antibody, although details of the results differed. The SIRS after SCI is a challenge to recovery and attenuation of the SIRS with an anti-integrin treatment is an important, clinically relevant finding.

Language: en