Temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury

Journal of Neuroinflammation

Research

M. Cristina Morganti-Kossmann¹  Bridgette D. Semple²  Sandy R. Shultz³  Larissa K. Dill⁴  Cheng Huang⁵  Ralf B. Schittenhelm⁵  Anup D. Shah⁶ 

[1] Department of Epidemiology & Preventive Medicine, Monash University, Prahran, VIC, Australia;Department of Child Health, Barrow Neurological Institute at Phoenix Children’s Hospital, Phoenix, AZ, USA;University of Arizona College of Medicine, Phoenix, AZ, USA;Department of Neuroscience, Monash University, Melbourne, VIC, Australia;Alfred Health, Prahran, VIC, Australia;Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Parkville, VIC, Australia;Department of Neuroscience, Monash University, Melbourne, VIC, Australia;Alfred Health, Prahran, VIC, Australia;Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Parkville, VIC, Australia;Health and Human Services, Vancouver Island University, Nanaimo, Canada;Department of Neuroscience, Monash University, Melbourne, VIC, Australia;Alfred Health, Prahran, VIC, Australia;The Perron Institute for Neurological and Translational Science, 6009, Nedlands, WA, Australia;Monash Proteomics and Metabolomics Facility, Monash University, Clayton, VIC, Australia;Monash Proteomics and Metabolomics Facility, Monash University, Clayton, VIC, Australia;Monash Bioinformatics Platform, Monash University, Clayton, VIC, Australia;

关键词: Protein;    Biomarker;    Inflammation;    TBI;    Secondary injury;    Neutrophil;   

DOI  :  10.1186/s12974-022-02654-0

 received in 2022-08-24, accepted in 2022-11-21,  发布年份 2022

来源: Springer

【 摘 要 】

The pathophysiology of traumatic brain injury (TBI) requires further characterization to fully elucidate changes in molecular pathways. Cerebrospinal fluid (CSF) provides a rich repository of brain-associated proteins. In this retrospective observational study, we implemented high-resolution mass spectrometry to evaluate changes to the CSF proteome after severe TBI. 91 CSF samples were analyzed with mass spectrometry, collected from 16 patients with severe TBI (mean 32 yrs; 81% male) on day 0, 1, 2, 4, 7 and/or 10 post-injury (8–16 samples/timepoint) and compared to CSF obtained from 11 non-injured controls. We quantified 1152 proteins with mass spectrometry, of which approximately 80% were associated with CSF. 1083 proteins were differentially regulated after TBI compared to control samples. The most highly-upregulated proteins at each timepoint included neutrophil elastase, myeloperoxidase, cathepsin G, matrix metalloproteinase-8, and S100 calcium-binding proteins A8, A9 and A12—all proteins involved in neutrophil activation, recruitment, and degranulation. Pathway enrichment analysis confirmed the robust upregulation of proteins associated with innate immune responses. Conversely, downregulated pathways included those involved in nervous system development, and several proteins not previously identified after TBI such as testican-1 and latrophilin-1. We also identified 7 proteins (GM2A, Calsyntenin 1, FAT2, GANAB, Lumican, NPTX1, SFRP2) positively associated with an unfavorable outcome at 6 months post-injury. Together, these findings highlight the robust innate immune response that occurs after severe TBI, supporting future studies to target neutrophil-related processes. In addition, the novel proteins we identified to be differentially regulated by severe TBI warrant further investigation as potential biomarkers of brain damage or therapeutic targets.

【 授权许可】

CC BY   
© The Author(s) 2022

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