MIC-1/GDF15 Overexpression Is Associated with Increased Functional Recovery in Traumatic Spinal Cord Injury.

Autor: Hassanpour Golakani M; St. Vincent's Centre for Applied Medical Research (AMR), St Vincent's Hospital and University of New South Wales (UNSW), Sydney, New South Wales, Australia.; The Neuroinflammation Research Group, Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia., Mohammad MG; Department of Medical Laboratory Sciences, College of Health Sciences and Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates. Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia., Li H; St. Vincent's Centre for Applied Medical Research (AMR), St Vincent's Hospital and University of New South Wales (UNSW), Sydney, New South Wales, Australia.; The Neuroinflammation Research Group, Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia., Gamble J; The Neuroinflammation Research Group, Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia., Breit SN; St. Vincent's Centre for Applied Medical Research (AMR), St Vincent's Hospital and University of New South Wales (UNSW), Sydney, New South Wales, Australia., Ruitenberg MJ; School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia., Brown DA; St. Vincent's Centre for Applied Medical Research (AMR), St Vincent's Hospital and University of New South Wales (UNSW), Sydney, New South Wales, Australia.; The Neuroinflammation Research Group, Centre for Immunology and Allergy Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.; Department of Immunopathology, Institute for Clinical Pathology and Medical Research-New South Wales Health Pathology, Westmead Hospital, Sydney, New South Wales, Australia.
Jazyk: angličtina
Zdroj: Journal of neurotrauma [J Neurotrauma] 2019 Dec 15; Vol. 36 (24), pp. 3410-3421. Date of Electronic Publication: 2019 Aug 01.
DOI: 10.1089/neu.2019.6421
Abstrakt: Spinal cord injury (SCI) has devastating consequences, with limited therapeutic options; therefore, improving its functional outcome is a major goal. The outcome of SCI is contributed to by neuroinflammation, which may be a target for improved recovery and quality of life after injury. Macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF15) has been identified as a potential novel therapy for central nervous system (CNS) injury because it is an immune regulatory cytokine with neurotrophic properties. Here we used MIC-1/GDF15 knockout (KO) and overexpressing/transgenic (Tg) and wild type (WT) animals to explore its putative therapeutic benefits in a mouse model of contusive SCI. MIC-1/GDF15 Tg mice had superior locomotor recovery and reduced secondary tissue loss at 28 days compared with their KO and WT counterparts. Overexpression of MIC-1/GDF15 coincided with increased expression of monocyte chemoattractant protein-1 (MCP-1)/C-C Motif Chemokine Ligand 2 (CCL2) at the lesion site (28 days post-SCI) and enhanced recruitment of inflammatory cells to the injured spinal cord. This inflammatory cellular infiltrate included an increased frequency of macrophages and dendritic cells (DCs) that mostly preceded recruitment of cluster of differentiation (CD)4 + and CD8 + T cells. Collectively, our findings suggest hat MIC-1/GDF15 is associated with beneficial changes in the clinical course of SCI that are characterized by altered post-injury inflammation and improved functional outcome. Further investigation of MIC-1/GDF15 as a novel therapeutic target for traumatic SCI appears warranted.
Databáze: MEDLINE