Dataset Information

Temporal proteomics of human cerebrospinal fluid reveals novel differentially-regulated proteins after severe traumatic brain injury

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 that may be affected by TBI. Here, 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. 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 or therapeutic targets.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebrospinal Fluid

SUBMITTER: Ralf Schittenhelm

LAB HEAD: Bridgette Semple

PROVIDER: PXD035289 | Pride | 2023-03-11

REPOSITORIES: Pride

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			Action	DRS
	F1CH20191206_set10_F1.raw	Raw
	F1CH20191206_set10_F10.raw	Raw
	F1CH20191206_set10_F11.raw	Raw
	F1CH20191206_set10_F12.raw	Raw
	F1CH20191206_set10_F2.raw	Raw

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Temporal proteomics of human cerebrospinal fluid after severe traumatic brain injury.

Shultz Sandy R SR Shah Anup D AD Huang Cheng C Dill Larissa K LK Schittenhelm Ralf B RB Morganti-Kossmann M Cristina MC Semple Bridgette D BD

Journal of neuroinflammation 20221208 1

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 ...[more]

PMID: 36482407

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