Multiplex array proteomics detects increased MMP-8 in CSF after spinal cord injury
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JOURNAL OF NEUROINFLAMMATION
RESEARCH
Open Access
Multiplex array proteomics detects increased MMP-8 in CSF after spinal cord injury Matthew Light1, Kenneth H Minor1, Peter DeWitt2, Kyle H Jasper1 and Stephen JA Davies1*
Abstract Introduction: A variety of methods have been used to study inflammatory changes in the acutely injured spinal cord. Recently novel multiplex assays have been used in an attempt to overcome limitations in numbers of available targets studied in a single experiment. Other technical challenges in developing pre-clinical rodent models to investigate biomarkers in cerebrospinal fluid (CSF) include relatively small volumes of sample and low concentrations of target proteins. The primary objective of this study was to characterize the inflammatory profile present in CSF at a subacute time point in a clinically relevant rodent model of traumatic spinal cord injury (SCI). Our other aim was to test a microarray proteomics platform specifically for this application. Methods: A 34 cytokine sandwich ELISA microarray was used to study inflammatory changes in CSF samples taken 12 days post-cervical SCI in adult rats. The difference between the median foreground signal and the median background signal was measured. Bonferroni and Benjamini-Hochburg multiple testing corrections were applied to limit the False Discovery Rate (FDR), and a linear mixed model was used to account for repeated measures in the array. Results: We report a novel subacute SCI biomarker, elevated levels of matrix metalloproteinase-8 protein in CSF, and discuss application of statistical models designed for multiplex testing. Conclusions: Major advantages of this assay over conventional methods include high-throughput format, good sensitivity, and reduced sample consumption. This method can be useful for creating comprehensive inflammatory profiles, and biomarkers can be used in the clinic to assess injury severity and to objectively grade response to therapy. Keywords: biomarker, cerebrospinal fluid (CSF), cytokine, inflammation, matrix metalloproteinase-8 (MMP-8), microarray, proteomics, spinal cord injury, tissue inhibitor of metalloproteinase-1 (TIMP-1).
Introduction Traumatic injury to the spinal cord can result in lifechanging neurological deficits. Patients, family members, clinicians, and researchers alike face significant longterm challenges including (but not limited to) pain management, rehabilitation, and functional improvement. According to 2011 estimates, the incidence of spinal cord injury (SCI) is roughly 12,000 cases per year in the USA, 40% resulting from motor vehicle accidents and 27% result from falls, creating a bimodal age distribution in * Correspondence: [email protected] 1 Department of Neurosurgery, University of Colorado School of Medicine, Building RC-1 North, Room P18-9400, 12800 E 19th Avenue, Aurora, CO 80045, USA Full list of author information is available at the end of the article
the patient population [1]. Long-term implications of these debilitating injuries are significant. Advanc
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