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Updated: Jul 17, 2026

Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Published on: May 27, 2022
A gel-based proteomic comparison of human cerebrospinal fluid between inflicted and non-inflicted pediatric traumatic
Wei-Min Gao1, Mandeep S Chadha, Rachel P Berger
1Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Insights
Inflicted traumatic brain injury (iTBI) in infants shows distinct cerebrospinal fluid (CSF) protein profiles compared to non-inflicted TBI. Proteomics identified key protein differences, aiding understanding of iTBI pathophysiology.
Area of Science:
- Neuroscience
- Biochemistry
- Proteomics
Background:
- Traumatic brain injury (TBI) is a leading cause of infant mortality, with inflicted TBI (iTBI) being the primary cause.
- Cerebrospinal fluid (CSF) protein composition changes with central nervous system pathologies, offering a window into brain injury.
- Understanding the differences between iTBI and non-inflicted TBI (nTBI) is crucial for diagnosis and treatment.
Purpose of the Study:
- To compare the CSF proteomic profiles of pediatric iTBI and nTBI patients.
- To identify specific proteins that differ between iTBI and nTBI.
- To explore potential biomarkers for differentiating inflicted from accidental TBI in infants.
Main Methods:
- Proteomic analysis using two-dimensional (2-D) difference in gel electrophoresis (DIGE) and mass spectrometry (MS).
- Comparison of pooled CSF samples from 13 pediatric iTBI and 13 nTBI patients with severe injuries.
- Analysis of approximately 250 protein spots with high inter-gel reproducibility (90%).
- Validation of key protein changes using Western blot.
Main Results:
- Haptoglobin (HP) isoforms were approximately fourfold higher in nTBI compared to iTBI.
- Prostaglandin D(2) synthase (PGDS) levels were 12-fold higher in iTBI versus nTBI.
- Cystatin C (CC) levels were sevenfold higher in iTBI versus nTBI.
- Confirmed significant differences in HP, PGDS, and CC between iTBI and nTBI groups.
Conclusions:
- Proteomic analysis of CSF reveals distinct protein signatures between iTBI and nTBI.
- Specific proteins like HP, PGDS, and CC may serve as biomarkers to differentiate injury types.
- These findings contribute to understanding the unique pathophysiology of iTBI and may aid in clinical diagnosis.
Abstract:
Traumatic brain injury (TBI) is the most common cause of traumatic death in infancy, and inflicted TBI (iTBI) is the predominant cause. Like other central nervous system pathologies, TBI changes the composition of cerebrospinal fluid (CSF), which may represent a unique clinical window on brain pathophysiology. Proteomic analysis, including two-dimensional (2-D) difference in gel electrophoresis (DIGE) combined with mass spectrometry (MS), was used to compare the CSF protein profile of two pooled samples from pediatric iTBI (n = 13) and non-inflicted TBI (nTBI; n = 13) patients with severe injury. CSF proteins from iTBI and nTBI were fluorescently labeled in triplicate using different fluorescent Cy dyes and separated by 2-D gel electrophoresis. Approximately 250 protein spots were found in CSF, with 90% between-gel reproducibility of the 2-D gel. Following in-gel digestion, the tryptic peptides were analyzed by MS for protein identification. The acute phase reactant, haptoglobin (HP) isoforms, showed an approximate fourfold increase in nTBI versus iTBI. In contrast, the levels of prostaglandin D(2) synthase (PGDS) and cystatin C (CC) were 12-fold and sevenfold higher in iTBI versus nTBI, respectively. The changes of HP, PGDS, and CC were confirmed by Western blot. These initial results with conventional gel-based proteomics show new protein changes that may ultimately help to understand pathophysiological differences between iTBI and nTBI.
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