Related Experiment Video
Updated: Feb 14, 2026
A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy
Published on: May 16, 2015
Plasma Biomarkers of Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy
An N Massaro1, Yvonne W Wu2, Theo K Bammler3
1Department of Pediatrics, The George Washington University School of Medicine and Children's National Health Systems, Washington, DC.
Insights
Elevated plasma biomarkers like Tau and BDNF in newborns with hypoxic-ischemic encephalopathy (HIE) indicate brain injury severity and predict neurodevelopmental outcomes. Erythropoietin (Epo) treatment effects require further investigation.
Area of Science:
- Neonatal neurology
- Biomarker discovery
- Neuroprotection research
Background:
- Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal brain injury.
- Identifying reliable biomarkers for HIE is crucial for early diagnosis and prognosis.
- Erythropoietin (Epo) is being investigated for its neuroprotective potential in HIE.
Purpose of the Study:
- To evaluate plasma brain-specific proteins and cytokines as biomarkers of brain injury in newborns with HIE.
- To assess the secondary effect of erythropoietin (Epo) treatment on the relationship between biomarkers and outcomes.
Main Methods:
- A phase II multicenter randomized trial evaluating Epo for neuroprotection in HIE.
- Plasma samples collected at baseline (<24 hours) and day 5.
- Brain injury assessed by MRI and neurodevelopmental assessments at 1 year.
Main Results:
- Elevated baseline S100B, Tau, UCH-L1, IL-1β, IL-6, IL-8, IL-10, IL-13, TNF-α, and IFN-γ levels correlated with increased brain injury severity by MRI.
- Higher baseline Tau and lower day 5 BDNF levels were associated with worse 1-year neurodevelopmental outcomes.
- No significant modification of biomarker relationships by Epo treatment was detected in this cohort.
Conclusions:
- Elevated plasma brain-specific proteins and cytokines in the first 24 hours are linked to worse MRI-confirmed brain injury in HIE newborns.
- Only Tau and BDNF levels showed a relationship with neurodevelopmental outcomes.
- Further research is needed to understand Epo's effect on biomarker-brain injury relationships in HIE.
Objectives:
To evaluate plasma brain specific proteins and cytokines as biomarkers of brain injury in newborns with hypoxic-ischemic encephalopathy (HIE) and, secondarily, to assess the effect of erythropoietin (Epo) treatment on the relationship between biomarkers and outcomes.
Study Design:
A study of candidate brain injury biomarkers was conducted in the context of a phase II multicenter randomized trial evaluating Epo for neuroprotection in HIE. Plasma was collected at baseline (<24 hours) and on day 5. Brain injury was assessed by magnetic resonance imaging (MRI) and neurodevelopmental assessments at 1 year. The relationships between Epo, brain-specific proteins (S100B, ubiquitin carboxy-terminal hydrolase-L1 [UCH-L1], total Tau, neuron specific enolase), cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, IL-12P70, IL-13, interferon-gamma [IFN-γ], tumor necrosis factor alpha [TNF-α], brain-derived neurotrophic factor [BDNF], monocyte chemoattractant protein-1), and brain injury were assessed.
Results:
In 50 newborns with encephalopathy, elevated baseline S100B, Tau, UCH-L1, IL-1β, IL-6, IL-8, IL-10, IL-13, TNF-α, and IFN-γ levels were associated with increasing brain injury severity by MRI. Higher baseline Tau and lower day 5 BDNF were associated with worse 1 year outcomes. No statistically significant evidence of Epo treatment modification on biomarkers was detected in this small cohort.
Conclusions:
Elevated plasma brain-specific proteins and cytokine levels in the first 24 hours of life are associated with worse brain injury by MRI in newborns with HIE. Only Tau and BDNF levels were found to be related to neurodevelopmental outcomes. The effect of Epo treatment on the relationships between biomarkers and brain injury in HIE requires further study.
Trial Registration:
ClinicalTrials.gov: 01913340.
Related Concept Videos
01:24Composition of Blood Plasma
01:17Ischemic Heart Disease: Overview
Atherosclerosis, the primary malefactor, orchestrates this dangerous condition. It manifests as the accumulation of fatty deposits, akin to insidious plaques, within arterial walls. As time elapses, these plaques metamorphose, hardening and...
01:22Enlargement of the Plasma Membrane
01:20Blood Studies for Cardiovascular System I: Cardiac Biomarkers
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...
01:27Plasma Membrane in Bacteria and Archaea
01:22Burn Injuries
The damage results in the death of skin cells, which can lead to a massive loss of fluid. Dehydration, electrolyte imbalance, and renal and circulatory failure follow, which can be fatal. Burn patients are treated with intravenous fluids to offset...