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Temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury.
Shultz, Sandy R; Shah, Anup D; Huang, Cheng; Dill, Larissa K; Schittenhelm, Ralf B; Morganti-Kossmann, M Cristina; Semple, Bridgette D.
Afiliação
  • Shultz SR; Department of Neuroscience, Monash University, Melbourne, VIC, Australia.
  • Shah AD; Alfred Health, Prahran, VIC, Australia.
  • Huang C; Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Parkville, VIC, Australia.
  • Dill LK; Health and Human Services, Vancouver Island University, Nanaimo, Canada.
  • Schittenhelm RB; Monash Proteomics and Metabolomics Facility, Monash University, Clayton, VIC, Australia.
  • Morganti-Kossmann MC; Monash Bioinformatics Platform, Monash University, Clayton, VIC, Australia.
  • Semple BD; Monash Proteomics and Metabolomics Facility, Monash University, Clayton, VIC, Australia.
J Neuroinflammation ; 19(1): 291, 2022 Dec 08.
Article em En | MEDLINE | ID: mdl-36482407
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteômica / Lesões Encefálicas Traumáticas Tipo de estudo: Observational_studies / Prognostic_studies Limite: Female / Humans / Male Idioma: En Revista: J Neuroinflammation Assunto da revista: NEUROLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Austrália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteômica / Lesões Encefálicas Traumáticas Tipo de estudo: Observational_studies / Prognostic_studies Limite: Female / Humans / Male Idioma: En Revista: J Neuroinflammation Assunto da revista: NEUROLOGIA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Austrália
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