The systemic inflammatory response after spinal cord injury damages lungs and kidneys

• Published in: Experimental neurology 2008-05, Vol.211 (1), p.259-270
• Main Authors: Gris, Denis, Hamilton, Eilis F., Weaver, Lynne C.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Apoptosis; Biological and medical sciences; Disease Models, Animal; Disease Progression; Flow Cytometry - methods; Inflammation; Inflammation - complications; Injuries of the nervous system and the skull. Diseases due to physical agents; Kidney - immunology; Kidney - metabolism; Kidney - pathology; Lipid Peroxidation; Lung - immunology; Lung - metabolism; Lung - pathology; Macrophage; Macrophages; Male; Malondialdehyde - metabolism; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Myeloperoxidase; Neurology; Neutrophil; Neutrophils; Organ damage; Oxidative burst; Peroxidase - metabolism; Proteinase; Rats; Rats, Wistar; Spinal Cord Compression - complications; Spinal Cord Compression - immunology; Thiobarbituric Acid Reactive Substances - metabolism; Time Factors; Traumas. Diseases due to physical agents; Treatment of spinal cord injury
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2008.01.033

Spinal cord injury (SCI) triggers a well characterized, acute, local inflammation leading to secondary damage at the lesion site. Another little recognized problem may be the activation of circulating inflammatory cells that potentially damage tissues outside the cord. We investigated this problem using severe clip-compression SCI in rats. We studied systemic inflammation after SCI and its effects on lungs and kidneys, as dysfunction of these organs is a frequent, early complication after SCI. From 2–24 h after SCI, the number of circulating neutrophils (especially immature cells) significantly increased by 3–10 fold. Flow cytometry experiments revealed that SCI transiently activates these neutrophils, causing increased oxidative responses to phorbolmyristic acid at 2 h after SCI; then, from 4–24 h, the neutrophils were less responsive. Neutrophil longevity was increased (30–50% decrease in apoptosis) at 2–8 h after SCI. Immunohistochemical analyses demonstrated the invasion of neutrophils into lungs and kidneys (2 h–7 d after SCI) and more phagocytic macrophages in lungs (12 h, 3 d after SCI). Myeloperoxidase and matrix metalloproteinase-9 activity in lung and kidney homogenates increased (12 h-7 d after SCI). Expression of COX-2 increased and lipid peroxidation also occurred within this time. Control experiments inducing local cord damage by excitotoxic quisqualate injection verified that SCI per se is sufficient to trigger systemic inflammation and organ damage. In summary, SCI mobilizes and activates neutrophils that then migrate into visceral organs, a phenomenon occurring in parallel with their well-known entry into the cord injury site. The systemic inflammatory response to SCI should be targeted in the development of new therapeutic strategies to treat SCI.