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Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Published on: May 27, 2022
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High-dimensional proteomic analysis for pathophysiological classification of traumatic brain injury
Lucia M Li1,2, Eleftheria Kodosaki3,4, Amanda Heslegrave3,4
1Department of Brain Sciences, Imperial College London, London W12 0BZ, UK.
Brain : a Journal of Neurology
|September 26, 2024
Summary
Novel proteomic analysis reveals distinct plasma protein changes in traumatic brain injury (TBI). These protein alterations correlate with specific injury patterns, offering new insights into TBI pathophysiology and potential for improved classification.
Area of Science:
- Neuroscience
- Biochemistry
- Medical Diagnostics
Background:
- Traumatic brain injury (TBI) presents complex and heterogeneous pathophysiology, with current classifications lacking informative insights.
- Proteomic approaches using fluid-based biomarkers offer a sensitive method for assessing a wide range of processes relevant to TBI.
- Novel high-dimensional, multiplex proteomic assays are crucial for exploring intricate disease mechanisms in TBI.
Purpose of the Study:
- To utilize novel high-dimensional, multiplex proteomic assays to identify altered plasma protein expression in acute TBI.
- To correlate proteomic findings with neuroimaging measures and explore potential TBI subgroups.
- To enhance the understanding of TBI pathophysiology and inform prognostication and treatment development.
Main Methods:
- Analysis of plasma samples from 88 participants (38 moderate-severe TBI, 22 non-TBI trauma, 28 controls) using Alamar NULISA™ CNS Diseases and OLINK® Target 96 Inflammation platforms.
- Measurement of established biomarkers (neurofilament light, GFAP, total tau, UCH-L1, S100B) alongside novel proteomic targets.
- Subacute MRI measures of lesion volume and white matter injury (fractional anisotropy) were obtained for a subset of participants.
Main Results:
- Differential expression analysis identified 16 proteins with TBI-specific plasma level changes, including neuronal, astroglial, neurodegenerative, and inflammatory markers.
- Acute plasma levels of UCH-L1, PSEN1, total tau, and pTau231 correlated with subacute lesion volume; Sequestome 1 and CCL2 correlated with white matter fractional anisotropy.
- Exploratory clustering identified three TBI subgroups based on protein expression, differing in injury patterns but not age or outcome.
Conclusions:
- TBI is associated with specific changes in acute plasma protein levels involved in neurodegeneration, inflammation, and cellular processes.
- These proteomic changes are linked to distinct injury patterns, indicating the relevance of studied processes in human TBI pathophysiology.
- Proteomic approaches hold promise for improving TBI classification, understanding, prognostication, and treatment development.
