title: Angiogenesis dysregulation in term asphyxiated newborns treated with hypothermia.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings suggest that angiogenesis pathways are dysregulated following birth asphyxia and are putatively involved in brain injury pathology and recovery.
authors.affiliation: Division of Newborn Medicine, Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
authors.forename: Henna
authors.initials: H
authors.lastname: Shaikh
authors.affiliation: Division of Newborn Medicine, Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
authors.forename: Elodie
authors.initials: E
authors.lastname: Boudes
authors.affiliation: Division of Newborn Medicine, Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
authors.forename: Zehra
authors.initials: Z
authors.lastname: Khoja
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Shevell
authors.affiliation: Division of Newborn Medicine, Department of Pediatrics, McGill University, Montreal, Quebec, Canada.
authors.forename: Pia
authors.initials: P
authors.lastname: Wintermark
mesh_terms: D001238:Asphyxia Neonatorum / Q000097:blood* / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D007231:Infant, Newborn; D008297:Male; D018919:Neovascularization, Physiologic / Q000502:physiology*
chemical_list: D015415:Biomarkers