CCL3 contributes to secondary damage after spinal cord injury
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(2020) 17:362
RESEARCH
Open Access
CCL3 contributes to secondary damage after spinal cord injury Nicolas Pelisch1,2, Jose Rosas Almanza1,2, Kyle E. Stehlik1,2, Brandy V. Aperi1,2 and Antje Kroner1,2,3*
Abstract Background: Secondary damage after spinal cord injury (SCI) is characterized by a cascade of events including hemorrhage, apoptosis, oxidative stress, and inflammation which increase the lesion size which can influence the functional impairment. Thus, identifying specific mechanisms attributed to secondary injury is critical in minimizing tissue damage and improving neurological outcome. In this work, we are investigating the role of CCL3 (macrophage inflammatory protein 1-α, MIP-1α), a chemokine involved in the recruitment of inflammatory cells, which plays an important role in inflammatory conditions of the central and peripheral nervous system. Methods: A mouse model of lower thoracic (T11) spinal cord contusion injury was used. We assessed expression levels of CCL3 and its receptors on the mRNA and protein level and analyzed changes in locomotor recovery and the inflammatory response in the injured spinal cord of wild-type and CCL3−/− mice. Results: The expression of CCL3 and its receptors was increased after thoracic contusion SCI in mice. We then examined the role of CCL3 after SCI and its direct influence on the inflammatory response, locomotor recovery and lesion size using CCL3−/− mice. CCL3−/− mice showed mild but significant improvement of locomotor recovery, a smaller lesion size and reduced neuronal damage compared to wild-type controls. In addition, neutrophil numbers as well as the pro-inflammatory cytokines and chemokines, known to play a deleterious role after SCI, were markedly reduced in the absence of CCL3. Conclusion: We have identified CCL3 as a potential target to modulate the inflammatory response and secondary damage after SCI. Collectively, this study shows that CCL3 contributes to progressive tissue damage and functional impairment during secondary injury after SCI. Keywords: CCL3, Spinal cord injury, Inflammation, Secondary damage
Background Spinal cord injury (SCI) is a debilitating neurological condition with an enormous impact on the health and quality of life of affected individuals. Despite intensive research efforts and clinical improvements in the past years, there is currently no cure for SCI, which thus continues to be a significant debilitating neurological * Correspondence: [email protected] 1 Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA 3 Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA Full list of author information is available at the end of the article
condition [1]. While the inflammatory response to the initial physical injury is essential for the clearance of cellular debris and tissue remodeling, excessive and unresolved inflammation after SCI can contribute to the secondary tissue damage and thus enhance functional impairment [2–4]. The cellular inflammatory environment
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