Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO
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 ne...
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Elsevier
2025-01-01
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| Series: | Neurotherapeutics |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878747924002083 |
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| author | Sue J. Hong Bradley J. De Souza Kristen K. Penberthy Lisa Hwang David E. Procaccini John N. Kheir Melania M. Bembea |
| author_facet | Sue J. Hong Bradley J. De Souza Kristen K. Penberthy Lisa Hwang David E. Procaccini John N. Kheir Melania M. Bembea |
| author_sort | Sue J. Hong |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6d035deedded4558a6010581d5fa869a |
| institution | Kabale University |
| issn | 1878-7479 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurotherapeutics |
| spelling | doaj-art-6d035deedded4558a6010581d5fa869a2025-02-01T04:11:55ZengElsevierNeurotherapeutics1878-74792025-01-01221e00521Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMOSue J. Hong0Bradley J. De Souza1Kristen K. Penberthy2Lisa Hwang3David E. Procaccini4John N. Kheir5Melania M. Bembea6Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Critical Care Medicine, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, CA, USADepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Pharmacy, Johns Hopkins Hospital, Baltimore, MD, USADepartment of Cardiology, Boston Children's Hospital, and the Department of Pediatrics, Harvard Medical School, Boston, MA, USADepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S1878747924002083Extracorporeal membrane oxygenationECMOChildBrain injuriesBiomarkers |
| spellingShingle | Sue J. Hong Bradley J. De Souza Kristen K. Penberthy Lisa Hwang David E. Procaccini John N. Kheir Melania M. Bembea Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO Neurotherapeutics Extracorporeal membrane oxygenation ECMO Child Brain injuries Biomarkers |
| title | Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO |
| title_full | Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO |
| title_fullStr | Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO |
| title_full_unstemmed | Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO |
| title_short | Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO |
| title_sort | plasma brain related biomarkers and potential therapeutic targets in pediatric ecmo |
| topic | Extracorporeal membrane oxygenation ECMO Child Brain injuries Biomarkers |
| url | http://www.sciencedirect.com/science/article/pii/S1878747924002083 |
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