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Updated: May 16, 2026
Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Published on: May 27, 2022
Inflammatory-neurodegenerative crosstalk in pediatric severe traumatic brain injury: a multi-domain plasma proteomic
Enis Cela1, Logan R Van Nynatten1,2, David Tweddell3
1Physiology & Pharmacology, Western University, London, ON, N6A 3K7, Canada.
Insights
This study reveals 67 differentially expressed proteins in pediatric severe traumatic brain injury (sTBI) plasma, highlighting inflammation and neurodegeneration links. These findings advance precision medicine for pediatric neurotrauma.
Area of Science:
- Neuroscience
- Biochemistry
- Pediatric Medicine
Background:
- Pediatric severe traumatic brain injury (sTBI) is a major cause of death and disability.
- Current molecular understanding of sTBI is limited, hindering effective treatment.
- Single-biomarker approaches cannot capture the complexity of sTBI's biological heterogeneity.
Purpose of the Study:
- To perform comprehensive proteomic profiling in pediatric sTBI.
- To identify clinical endotypes by analyzing plasma proteins across neuropathologic domains.
- To investigate acute-phase neuro-proteomic changes in pediatric sTBI.
Main Methods:
- An exploratory case-control study involving 23 pediatric sTBI patients and 20 healthy controls.
- Plasma samples collected on days 1 and 3 post-admission to the pediatric intensive care unit (PICU).
- High-throughput proteomic analysis quantified 120 proteins across five neuropathologic domains using the Nucleic Acid-Linked Immuno-Sandwich Assay.
Main Results:
- 67 differentially expressed proteins (DEPs) identified on PICU Day 1, with 46 increased and 21 decreased.
- Inflammatory mediators dominated the response, including acute-phase reactants and cytokines (e.g., IL-6, CRP).
- Network analysis indicated IL-6 as a central hub connecting inflammatory and neurodegenerative pathways; correlations with clinical outcomes were observed.
Conclusions:
- This study presents the first multi-domain neuro-proteomic characterization of acute pediatric sTBI.
- Identified DEPs and network analyses reveal co-enrichment of inflammatory and neurodegeneration programs.
- Findings support biomarker validation and inform precision medicine strategies for pediatric neurotrauma.
Background:
Pediatric severe traumatic brain injury (sTBI) remains a leading cause of death and long-term disability, yet its molecular characterization is incomplete. Single-biomarker approaches fail to capture the biological heterogeneity underlying variable clinical outcomes. Comprehensive proteomic profiling across neuropathologic domains to identify clinical endotypes has not been performed in pediatric sTBI. This study addresses this gap using high-throughput plasma neuro-proteomic profiling during the acute injury phase.
Methods:
We conducted an exploratory case-control study enrolling 23 pediatric sTBI patients (median age 15 years, 70% male) admitted to a Level 1 Trauma Center and 20 age- and sex-matched healthy controls. Plasma samples were collected on pediatric intensive care unit (PICU) Day 1 and Day 3. Proteomic analysis using the Nucleic Acid-Linked Immuno-Sandwich Assay quantified 120 proteins spanning five neuropathologic domains: neuroinflammation, neurodegeneration, amyloid/tau pathology, synaptic regulation, and vascular/metabolic pathways. Differential expression analysis identified dysregulated proteins in sTBI, facilitating interrogation of protein-protein interaction networks and protein-clinical variable correlations.
Results:
Proteomic analysis on PICU Day 1 identified 67 differentially expressed proteins (DEPs): 46 increased and 21 decreased. Inflammatory mediators (n = 31/51) dominated the response, with marked elevations in acute-phase reactants (SAA1, CRP), pro-inflammatory cytokines (IL-6, IL-33), and the anti-inflammatory marker IL-10. Network analysis revealed IL-6 as a central hub linking inflammatory and neurodegenerative pathways. Brain-specific proteins showed distinct temporal patterns: CRH, GFAP, S100B, pTau-231, pTau-181, REST, and TAFA5 displayed biphasic trajectories, whereas NEFH, NEFL, and NGF exhibited sustained increases through PICU Day 3. Enrichment analyses localized DEPs predominantly to inflammatory or neuronal compartments and tissues. Significant correlations emerged between multiple proteins and clinical outcomes.
Conclusions:
This exploratory study provides the first comprehensive, multi-domain neuro-proteomic characterization of acute pediatric sTBI, revealing molecular disruptions beyond the scope of traditional single-biomarker approaches. We identified 67 DEPs spanning five neuropathologic domains, with network analysis revealing co-enrichment of inflammatory and neurodegeneration-related programs, consistent with known connectivity patterns. These findings establish a biological foundation for biomarker validation studies and inform precision medicine strategies in pediatric neurotrauma.
Related Concept Videos
01:28Traumatic Brain Injury l: Introduction
01:22Cerebral Edema ll: Pathophysiology