The Cerebrospinal Fluid Proteomic Response to Traumatic and Nontraumatic Acute Brain Injury: A Prospective Study.
Biomarker
Complement
Gene ontology
Pathophysiological pathways
Proteomic analysis
Journal
Neurocritical care
ISSN: 1556-0961
Titre abrégé: Neurocrit Care
Pays: United States
ID NLM: 101156086
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
29
10
2021
accepted:
01
04
2022
pubmed:
7
5
2022
medline:
1
10
2022
entrez:
6
5
2022
Statut:
ppublish
Résumé
Quantitative analysis of ventricular cerebrospinal fluid (vCSF) proteins following acute brain injury (ABI) may help identify pathophysiological pathways and potential biomarkers that can predict unfavorable outcome. In this prospective proteomic analysis study, consecutive patients with severe ABI expected to require intraventricular catheterization for intracranial pressure (ICP) monitoring for at least 5 days and patients without ABI admitted for elective clipping of an unruptured cerebral aneurysm were included. vCSF samples were collected within the first 24 h after ABI and ventriculostomy insertion and then every 24 h for 5 days. In patients without ABI, a single vCSF sample was collected at the time of elective clipping. Data-independent acquisition and sequential window acquisition of all theoretical spectra (SWATH) mass spectrometry were used to compare differences in protein expression in patients with ABI and patients without ABI and in patients with traumatic and nontraumatic ABI. Differences in protein expression according to different ICP values, intensive care unit outcome, subarachnoid hemorrhage (SAH) versus traumatic brain injury (TBI), and good versus poor 3-month functional status (assessed by using the Glasgow Outcome Scale) were also evaluated. vCSF proteins with significant differences between groups were compared by using linear models and selected for gene ontology analysis using R Language and the Panther database. We included 50 patients with ABI (SAH n = 23, TBI n = 15, intracranial hemorrhage n = 6, ischemic stroke n = 3, others n = 3) and 12 patients without ABI. There were significant differences in the expression of 255 proteins between patients with and without ABI (p < 0.01). There were intraday and interday differences in expression of seven proteins related to increased inflammation, apoptosis, oxidative stress, and cellular response to hypoxia and injury. Among these, glial fibrillary acidic protein expression was higher in patients with ABI with severe intracranial hypertension (ICH) (ICP ≥ 30 mm Hg) or death compared to those without (log 2 fold change: + 2.4; p < 0.001), suggesting extensive primary astroglial injury or death. There were differences in the expression of 96 proteins between patients with traumatic and nontraumatic ABI (p < 0.05); intraday and interday differences were observed for six proteins related to structural damage, complement activation, and cholesterol metabolism. Thirty-nine vCSF proteins were associated with an increased risk of severe ICH (ICP ≥ 30 mm Hg) in patients with traumatic compared with nontraumatic ABI (p < 0.05). No significant differences were found in protein expression between patients with SAH versus TBI or between those with good versus poor 3-month Glasgow Outcome Scale score. Dysregulated vCSF protein expression after ABI may be associated with an increased risk of severe ICH and death.
Sections du résumé
BACKGROUND
Quantitative analysis of ventricular cerebrospinal fluid (vCSF) proteins following acute brain injury (ABI) may help identify pathophysiological pathways and potential biomarkers that can predict unfavorable outcome.
METHODS
In this prospective proteomic analysis study, consecutive patients with severe ABI expected to require intraventricular catheterization for intracranial pressure (ICP) monitoring for at least 5 days and patients without ABI admitted for elective clipping of an unruptured cerebral aneurysm were included. vCSF samples were collected within the first 24 h after ABI and ventriculostomy insertion and then every 24 h for 5 days. In patients without ABI, a single vCSF sample was collected at the time of elective clipping. Data-independent acquisition and sequential window acquisition of all theoretical spectra (SWATH) mass spectrometry were used to compare differences in protein expression in patients with ABI and patients without ABI and in patients with traumatic and nontraumatic ABI. Differences in protein expression according to different ICP values, intensive care unit outcome, subarachnoid hemorrhage (SAH) versus traumatic brain injury (TBI), and good versus poor 3-month functional status (assessed by using the Glasgow Outcome Scale) were also evaluated. vCSF proteins with significant differences between groups were compared by using linear models and selected for gene ontology analysis using R Language and the Panther database.
RESULTS
We included 50 patients with ABI (SAH n = 23, TBI n = 15, intracranial hemorrhage n = 6, ischemic stroke n = 3, others n = 3) and 12 patients without ABI. There were significant differences in the expression of 255 proteins between patients with and without ABI (p < 0.01). There were intraday and interday differences in expression of seven proteins related to increased inflammation, apoptosis, oxidative stress, and cellular response to hypoxia and injury. Among these, glial fibrillary acidic protein expression was higher in patients with ABI with severe intracranial hypertension (ICH) (ICP ≥ 30 mm Hg) or death compared to those without (log 2 fold change: + 2.4; p < 0.001), suggesting extensive primary astroglial injury or death. There were differences in the expression of 96 proteins between patients with traumatic and nontraumatic ABI (p < 0.05); intraday and interday differences were observed for six proteins related to structural damage, complement activation, and cholesterol metabolism. Thirty-nine vCSF proteins were associated with an increased risk of severe ICH (ICP ≥ 30 mm Hg) in patients with traumatic compared with nontraumatic ABI (p < 0.05). No significant differences were found in protein expression between patients with SAH versus TBI or between those with good versus poor 3-month Glasgow Outcome Scale score.
CONCLUSIONS
Dysregulated vCSF protein expression after ABI may be associated with an increased risk of severe ICH and death.
Identifiants
pubmed: 35523916
doi: 10.1007/s12028-022-01507-1
pii: 10.1007/s12028-022-01507-1
doi:
Substances chimiques
Biomarkers
0
Glial Fibrillary Acidic Protein
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
463-470Informations de copyright
© 2022. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.
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