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Early Pathological and Magnetic Resonance Detection of Cerebral Injury Using a Rat Model of Neonatal Hypoxic Ischemic Encephalopathy
Published on: October 28, 2022
Blood Biomarkers for Evaluation of Perinatal Encephalopathy
Ernest M Graham1, Irina Burd2, Allen D Everett3
1Division of Maternal-Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of MedicineBaltimore, MD, USA; Neuroscience Intensive Care Nursery Program, Johns Hopkins University School of MedicineBaltimore, MD, USA.
Insights
New blood biomarkers, including brain exosomes, show promise for identifying fetal and neonatal brain injury. This "liquid brain biopsy" could improve diagnosis and treatment compared to current methods.
Area of Science:
- Neuroscience
- Biomarkers
- Neonatal Research
Background:
- Traumatic brain injury (TBI) and perinatal hypoxic-ischemic encephalopathy (HIE) share pathological features.
- Both conditions involve hypoxia, excitotoxicity, oxidative stress, and inflammation.
- Blood-brain barrier disruption allows central nervous system substances to enter peripheral circulation.
Purpose of the Study:
- To explore blood-based biomarkers for identifying fetal and neonatal brain injury.
- To investigate the potential of brain exosomes as diagnostic tools.
- To improve upon current imprecise methods for diagnosing perinatal brain injury.
Main Methods:
- Review of recent research on blood biomarkers for brain injury.
- Focus on shared mechanisms between TBI and HIE.
- Evaluation of brain exosomes as potential biomarker carriers.
- Concept of "liquid brain biopsy" for fetal and neonatal assessment.
Main Results:
- Shared biomarkers include excitatory amino acids, lipid peroxidation products, microRNAs, and inflammatory markers.
- Brain exosomes protect transported molecules from degradation, making them ideal biomarker containers.
- A multiplex of serum biomarkers could offer more precise identification of brain injury.
Conclusions:
- Blood biomarkers, particularly brain exosomes, offer a promising non-invasive approach for diagnosing fetal and neonatal brain injury.
- Quantitative biomarker measurements can guide clinical decisions, including operative delivery and treatment effectiveness.
- The "liquid brain biopsy" concept represents a significant advancement in perinatal neurology.
Abstract:
Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products, and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the "liquid brain biopsy." A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.

