Journal
EXPERIMENTAL NEUROLOGY
Volume 215, Issue 2, Pages 308-316Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2008.10.022
Keywords
Inflammation; Oxidative damage; Neutrophil; Macrophage; Oxidative enzyme; Trauma
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Funding
- New Emerging Team grant from the Canadian Institutes of Health Research [RMN63187]
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Traumatic injury can cause a systemic inflammatory response, increasing oxidative activity of circulating leukocytes and potentially exacerbating the original injury, as well as causing damage to initially unaffected organs. Although the importance of intraspinal inflammation after human spinal cord injury is appreciated, the role of the systemic inflammatory response to this injury is not widely recognised. We investigated oxidative activity of blood leukocytes from nine cord-injured subjects and six trauma controls (bone fractures without CNS injury) at 6 h-2 weeks after injury, comparing values to those of ten uninjured Subjects. Neutrophil and monocyte free radical production, evaluated by flow cytometry, increased significantly more in cord injury subjects than in trauma controls (6-fold vs 50% increases). In leukocyte homogenates, the concentration of free radicals increased significantly more in cord injury subjects (2-fold) than in the trauma controls (1.6-fold) as did activity of myeloperoxidase (2.3-fold vs. 1.7-fold). Moreover, in homogenates and blood smears, expression of the NADPH oxidase subunit gp91(phox) and of the oxidative enzyme, inducible nitric oxide synthetase was 20-25% greater in cord injury subjects than in trauma controls. Expression of the pro-inflarnmatory transcription factor NF-kappa B and of cyclooxygenase-2 increased similarly after both injuries. Finally, aldehyde products of tissue-damaging lipid peroxidation also increased significantly more in the plasma of spinal cord injury subjects than in trauma controls (2.6 fold vs. 1.9-fold). Spinal cord injury causes a particularly intense systemic inflammatory response. Limiting this response briefly after cord injury should protect the spinal cord and tissues/organs outside the CNS from secondary damage. (c) 2008 Elsevier Inc. All rights reserved.
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