Journal Article

Angiogenesis Dysregulation in Term Asphyxiated Newborns Treated with Hypothermia

Khoja, Zehra, Shaikh, Henna, Wintermark, Pia, Boudes, Elodie, Shevell, Michael

2015

Overview

Neonatal encephalopathy following birth asphyxia is a major predictor of long-term neurological impairment. Therapeutic hypothermia is currently the standard of care to prevent brain injury in asphyxiated newborns but is not protective in all cases. More robust and versatile treatment options are needed. Angiogenesis is a demonstrated therapeutic target in adult stroke. However, no systematic study examines the expression of angiogenesis-related markers following birth asphyxia in human newborns. This study aimed to evaluate the expression of angiogenesis-related protein markers in asphyxiated newborns developing and not developing brain injury compared to healthy control newborns. Twelve asphyxiated newborns treated with hypothermia were prospectively enrolled; six developed eventual brain injury and six did not. Four healthy control newborns were also included. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study the plasma concentration of 49 angiogenesis-related proteins. Mean protein concentrations were compared between each group of newborns. Compared to healthy newborns, asphyxiated newborns not developing brain injury showed up-regulation of pro-angiogenic proteins, including fatty acid binding protein-4, glucose-6-phosphate isomerase, neuropilin-1, and receptor tyrosine-protein kinase erbB-3; this up-regulation was not evident in asphyxiated newborns eventually developing brain injury. Also, asphyxiated newborns developing brain injury showed a decreased expression of anti-angiogenic proteins, including insulin-growth factor binding proteins -1, -4, and -6, compared to healthy newborns. These findings suggest that angiogenesis pathways are dysregulated following birth asphyxia and are putatively involved in brain injury pathology and recovery.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Angiogenesis / Asphyxia / Asphyxia Neonatorum - blood / Asphyxia Neonatorum - therapy / Biomarkers - blood / Birth weight / Blood-brain barrier / Brain / Brain injury / Brain research / Care and treatment / Childbirth & labor / Comparative analysis / Control / Control methods / Encephalopathy / ErbB protein / ErbB-3 protein / Extracellular matrix / Fatty acid-binding protein / Fatty acids / Female / Genetic aspects / Glucose isomerase / Glucose-6-phosphate isomerase / Growth factors / Head injuries / Health aspects / Humans / Hypothermia / Hypothermia, Induced / Hypoxia / Infant, Newborn / Injury prevention / Insulin / Ischemia / Kinases / Male / Markers / Medicine / Neonates / Neovascularization / Neovascularization, Physiologic - physiology / Neurological complications / Neuropilin / Newborn babies / NMR / Nuclear magnetic resonance / Pediatrics / Phosphates / Physiological aspects / Protein arrays / Protein kinase / Proteins / Rodents / Stroke / Traumatic brain injury / Tyrosine / Vascular endothelial growth factor