Faculty Collaboration Database

CCL3 contributes to secondary damage after spinal cord injury. J Neuroinflammation 2020 Nov 27;17(1):362

Date

11/29/2020

Pubmed ID

33246483

Pubmed Central ID

PMC7694914

DOI

10.1186/s12974-020-02037-3

Scopus ID

2-s2.0-85096689144 (requires institutional sign-in at Scopus site)   46 Citations

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.

Author List

Pelisch N, Rosas Almanza J, Stehlik KE, Aperi BV, Kroner A

Author

Antje Kroner-Milsch MD, PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Chemokine CCL3
Inflammation
Mice
Mice, Inbred C57BL
Mice, Knockout
Recovery of Function
Spinal Cord Injuries