vCSF Danger-associated Molecular Patterns After Traumatic and Nontraumatic Acute Brain Injury: A Prospective Study.
Journal
Journal of neurosurgical anesthesiology
ISSN: 1537-1921
Titre abrégé: J Neurosurg Anesthesiol
Pays: United States
ID NLM: 8910749
Informations de publication
Date de publication:
27 Apr 2023
27 Apr 2023
Historique:
received:
15
10
2022
accepted:
14
03
2023
medline:
16
5
2023
pubmed:
16
5
2023
entrez:
15
5
2023
Statut:
aheadofprint
Résumé
Danger-associated molecular patterns (DAMPs) may be implicated in the pathophysiological pathways associated with an unfavorable outcome after acute brain injury (ABI). We collected samples of ventricular cerebrospinal fluid (vCSF) for 5 days in 50 consecutive patients at risk of intracranial hypertension after traumatic and nontraumatic ABI. Differences in vCSF protein expression over time were evaluated using linear models and selected for functional network analysis using the PANTHER and STRING databases. The primary exposure of interest was the type of brain injury (traumatic vs. nontraumatic), and the primary outcome was the vCSF expression of DAMPs. Secondary exposures of interest included the occurrence of intracranial pressure ≥20 or ≥ 30 mm Hg during the 5 days post-ABI, intensive care unit (ICU) mortality, and neurological outcome (assessed using the Glasgow Outcome Score) at 3 months post-ICU discharge. Secondary outcomes included associations of these exposures with the vCSF expression of DAMPs. A network of 6 DAMPs (DAMP_trauma; protein-protein interaction [PPI] P=0.04) was differentially expressed in patients with ABI of traumatic origin compared with those with nontraumatic ABI. ABI patients with intracranial pressure ≥30 mm Hg differentially expressed a set of 38 DAMPS (DAMP_ICP30; PPI P< 0.001). Proteins in DAMP_ICP30 are involved in cellular proteolysis, complement pathway activation, and post-translational modifications. There were no relationships between DAMP expression and ICU mortality or unfavorable versus favorable outcomes. Specific patterns of vCSF DAMP expression differentiated between traumatic and nontraumatic types of ABI and were associated with increased episodes of severe intracranial hypertension.
Sections du résumé
BACKGROUND
BACKGROUND
Danger-associated molecular patterns (DAMPs) may be implicated in the pathophysiological pathways associated with an unfavorable outcome after acute brain injury (ABI).
METHODS
METHODS
We collected samples of ventricular cerebrospinal fluid (vCSF) for 5 days in 50 consecutive patients at risk of intracranial hypertension after traumatic and nontraumatic ABI. Differences in vCSF protein expression over time were evaluated using linear models and selected for functional network analysis using the PANTHER and STRING databases. The primary exposure of interest was the type of brain injury (traumatic vs. nontraumatic), and the primary outcome was the vCSF expression of DAMPs. Secondary exposures of interest included the occurrence of intracranial pressure ≥20 or ≥ 30 mm Hg during the 5 days post-ABI, intensive care unit (ICU) mortality, and neurological outcome (assessed using the Glasgow Outcome Score) at 3 months post-ICU discharge. Secondary outcomes included associations of these exposures with the vCSF expression of DAMPs.
RESULTS
RESULTS
A network of 6 DAMPs (DAMP_trauma; protein-protein interaction [PPI] P=0.04) was differentially expressed in patients with ABI of traumatic origin compared with those with nontraumatic ABI. ABI patients with intracranial pressure ≥30 mm Hg differentially expressed a set of 38 DAMPS (DAMP_ICP30; PPI P< 0.001). Proteins in DAMP_ICP30 are involved in cellular proteolysis, complement pathway activation, and post-translational modifications. There were no relationships between DAMP expression and ICU mortality or unfavorable versus favorable outcomes.
CONCLUSIONS
CONCLUSIONS
Specific patterns of vCSF DAMP expression differentiated between traumatic and nontraumatic types of ABI and were associated with increased episodes of severe intracranial hypertension.
Identifiants
pubmed: 37188652
doi: 10.1097/ANA.0000000000000916
pii: 00008506-990000000-00060
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
D.C. is a Senior Research Associate at the FRS-FNRS. The remaining authors have no conflicts of interest to disclose.
Références
Braun P, Gingras AC. History of protein-protein interactions: from egg-white to complex networks. Proteomics. 2012;12:1478–1498.
Schenck EJ, Ma KC, Murthy SB, et al. Danger signals in the ICU. Crit Care Med. 2018;46:791–798.
Iyer SS, Pulskens WP, Sadler JJ, et al. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc Natl Acad Sci USA. 2009;106:20388–20393.
Lord JM, Midwinter MJ, Chen YF, et al. The systemic immune response to trauma: an overview of pathophysiology and treatment. Lancet. 2014;384:1455–1465.
Sonnemann KJ, Bement WM. Wound repair: toward understanding and integration of single-cell and multicellular wound responses. Annu Rev Cell Dev Biol. 2011;27:237–263.
Kofke WA, Rajagopalan S, Ayubcha D, et al. Defining a taxonomy of intracranial hypertension: is ICP more than just a number? J Neurosurg Anesthesiol. 2020;32:120–131.
Nathan C. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol. 2006;6:173–182.
Santacruz CA, Vincent JL, Bader A, et al. Association of cerebrospinal fluid protein biomarkers with outcomes in patients with traumatic and non-traumatic acute brain injury: systematic review of the literature. Crit Care. 2021;25:278.
Santacruz CA, Vincent JL, Duitama J, et al. The cerebrospinal fluid proteomic response to traumatic and nontraumatic acute brain injury: a prospective study. Neurocrit Care. 2022;37:463–470.
Gordillo-Escobar E, Egea-Guerrero JJ, Rodríguez-Rodríguez A, et al. Usefulness of biomarkers in the prognosis of severe head injuries. Med Intensiva. 2016;40:105–112.
Kurowski BG, Treble-Barna A, Pitzer AJ, et al. Applying systems biology methodology to identify genetic factors possibly associated with recovery after traumatic brain injury. J Neurotrauma. 2017;34:2280–2290.
Feala JD, Abdulhameed MD, Yu C, et al. Systems biology approaches for discovering biomarkers for traumatic brain injury. J Neurotrauma. 2013;30:1101–1116.
Aben HP, Biessels GJ, Weaver NA, et al., PROCRAS Study Group. Extent to which network hubs are affected by ischemic stroke predicts cognitive recovery. Stroke. 2019;50:2768–2774.
Banoei MM, Casault C, Metwaly SM, et al. Metabolomics and biomarker discovery in traumatic brain Injury. J Neurotrauma. 2018;35:1831–1848.
Yanagida M. Functional proteomics; current achievements. J Chromatogr B Analyt Technol Biomed Life Sci. 2002;771:89–106.
Berggård T, Linse S, James P. Methods for the detection and analysis of protein-protein interactions. Proteomics. 2007;7:2833–2842.
von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61:344–349.
Schaefer L. Complexity of danger: the diverse nature of damage-associated molecular patterns. J Biol Chem. 2014;289:35237–35245.
Wang S, Song R, Wang Z, et al. S100A8/A9 in inflammation. Front Immunol. 2018;9:1298.
Hammad A, Westacott L, Zaben M. The role of the complement system in traumatic brain injury: a review. J Neuroinflammation. 2018;15:24.
Ravasz E. Detecting hierarchical modularity in biological networks. Methods Mol Biol. 2009;541:145–160.
Reeves TM, Greer JE, Vanderveer AS, et al. Proteolysis of submembrane cytoskeletal proteins ankyrin-G and αII-spectrin following diffuse brain injury: a role in white matter vulnerability at Nodes of Ranvier. Brain Pathol. 2010;20:1055–1068.
Yang YS, Wang CC, Chen BH, et al. Tyrosine sulfation as a protein post-translational modification. Molecules. 2015;20:2138–2164.
Sun F, Suttapitugsakul S, Xiao H, et al. Comprehensive analysis of protein glycation reveals its potential impacts on protein degradation and gene expression in human cells. J Am Soc Mass Spectrom. 2019;30:2480–2490.
Gao TL, Yuan XT, Yang D, et al. Expression of HMGB1 and RAGE in rat and human brains after traumatic brain injury. J Trauma Acute Care Surg. 2012;72:643–649.
Sun S, Sursal T, Adibnia Y, et al. Mitochondrial DAMPs increase endothelial permeability through neutrophil dependent and independent pathways. PLoS One. 2013;8:e59989.
Relja B, Land WG. Damage-associated molecular patterns in trauma. Eur J Trauma Emerg Surg. 2020;46:751–775.
Muhammad S, Chaudhry SR, Kahlert UD, et al. Brain immune interactions-novel emerging options to treat acute ischemic brain injury. Cells. 2021;10:2429.
Pavlopoulos GA, Secrier M, Moschopoulos CN, et al. Using graph theory to analyze biological networks. BioData Min. 2011;4:10.
Kofke WA, Ren Y, Augoustides JG, et al. Reframing the biological basis of neuroprotection using functional genomics: differentially weighted, time-dependent multifactor pathogenesis of human ischemic brain damage. Front Neurol. 2018;9:497.
Kofke WA. Incrementally applied multifaceted therapeutic bundles in neuroprotection clinical trials…time for change. Neurocrit Care. 2010;12:438–444.
Weaver SM, Chau A, Portelli JN, et al. Genetic polymorphisms influence recovery from traumatic brain injury. Neuroscientist. 2012;18:631–644.
Gillet LC, Navarro P, Tate S, et al. Targeted data extraction of the MS/MS spectra generated by data-independent acquisition: a new concept for consistent and accurate proteome analysis. Mol Cell Proteomics. 2012;11:O111.016717.
Aasebø E, Opsahl JA, Bjørlykke Y, et al. Effects of blood contamination and the rostro-caudal gradient on the human cerebrospinal fluid proteome. PLoS One. 2014;9:e90429.