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Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO
Sue J Hong1, Bradley J De Souza2, Kristen K Penberthy1
1Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Insights
Extracorporeal membrane oxygenation (ECMO) can cause acute brain injury (ABI). Plasma biomarkers help identify brain injury risk, diagnose ABI, and predict outcomes in ECMO patients.
Area of Science:
- Neuroscience
- Cardiovascular Medicine
- Biomarker Discovery
Background:
- Extracorporeal membrane oxygenation (ECMO) supports severe cardiopulmonary failure but carries a high risk of acute brain injury (ABI).
- Mechanisms of ABI in ECMO include direct cellular injury, blood-brain barrier (BBB) dysfunction, systemic inflammation, neuroinflammation, and coagulopathy.
- Plasma biomarkers are increasingly utilized to assess ABI risk, diagnosis, and prognosis in ECMO patients.
Purpose of the Study:
- To review the role of plasma biomarkers in understanding and managing acute brain injury (ABI) in patients undergoing extracorporeal membrane oxygenation (ECMO).
- To identify specific biomarkers associated with neurovascular injury, BBB dysfunction, inflammation, and coagulopathy in the context of ECMO.
- To explore how biomarker analysis can inform neuroprotective strategies and therapeutic targets.
Main Methods:
- Review of existing literature on plasma biomarkers and acute brain injury in ECMO.
- Analysis of studies measuring CNS-derived proteins (NSE, tau, GFAP, S100β) and BBB components (vWF, PDGFRβ) in plasma.
- Examination of pro-inflammatory cytokines (IL-1β, IL-6, IFN-γ, TNF-α) and coagulation profiles in relation to neuroimaging and outcomes.
Main Results:
- Elevated levels of NSE, tau, GFAP, and S100β indicate neuronal and astroglial injury and are linked to poorer outcomes.
- Evidence of BBB breakdown (detected via NSE, GFAP, S100β, vWF, PDGFRβ) correlates with increased mortality and worse neurofunctional outcomes.
- Higher pro-inflammatory cytokine concentrations are associated with abnormal neuroimaging, and distinct coagulation and inflammatory responses are observed.
Conclusions:
- Plasma biomarkers are crucial for risk stratification, diagnosis, and prognostication of ABI in ECMO patients.
- Biomarker analysis provides insights into the complex mechanisms of neurovascular injury during ECMO.
- Understanding these biomarkers can guide the development of targeted neuroprotective strategies and therapies.
Abstract:
Extracorporeal membrane oxygenation (ECMO) is a technique used to support severe cardiopulmonary failure. Its potential life-saving benefits are tempered by the significant risk for acute brain injury (ABI), from both primary pathophysiologic factors and ECMO-related complications through central nervous system cellular injury, blood-brain barrier dysfunction (BBB), systemic inflammation and neuroinflammation, and coagulopathy. Plasma biomarkers are an emerging tool used to stratify risk for and diagnose ABI, and prognosticate neurofunctional outcomes. Components of the neurovascular unit have been rational targets for this inquiry in ECMO. Central nervous system (CNS) neuronal and astroglial cellular-derived neuron-specific enolase (NSE), tau, glial fibrillary acidic protein (GFAP) and S100β elevations have been detected in ABI and are associated with poorer outcomes. Evidence of BBB breakdown through peripheral blood detection of CNS cellular components NSE, GFAP, and S100β, as well as evidence of elevated BBB components vWF and PDGFRβ are associated with higher mortality and worse neurofunctional outcomes. Higher concentrations of pro-inflammatory cytokines (IL-1β, IL-6, IFN-γ, TNF-α) are associated with abnormal neuroimaging, and proteomic expression panels reveal different coagulation and inflammatory responses. Abnormal coagulation profiles are common in ECMO with ongoing studies attempting to describe specific abnormalities either being causal or associated with neurologic outcomes; vWF has shown some promise. Understanding these mechanisms of injury through biomarker analysis supports potential neuroprotective strategies such as individualized blood pressure targets, judicious hypercarbia and hypoxemia correction, and immunomodulation (inhaled hydrogen and N-acetylcysteine). Further research continues to elucidate the role of biomarkers as predictors, prognosticators, and therapeutic targets.
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