Abstract
BackgroundNeonatal 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.ObjectiveThis 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.Design/MethodsTwelve 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.ResultsCompared 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.ConclusionsThese findings suggest that angiogenesis pathways are dysregulated following birth asphyxia and are putatively involved in brain injury pathology and recovery.
Highlights
In angiogenesis, a coordinated orchestra of proteins causes new blood vessels to sprout and mature from existing vessels
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
Summary
A coordinated orchestra of proteins causes new blood vessels to sprout and mature from existing vessels. This process begins with the degradation of the local extracellular matrix and the weakening of tight junctions and interactions between endothelial cells and pericytes. Recent studies of adult stroke highlight angiogenesis as a potential therapeutic target. Enhanced angiogenesis is accompanied by enhanced neurogenesis and improved neurological recovery in animal models of adult stroke [2,3,4] and is correlated with improved outcomes in human adults [5]. Angiogenesis is a demonstrated therapeutic target in adult stroke. No systematic study examines the expression of angiogenesisrelated markers following birth asphyxia in human newborns
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