title: New insights into the pathogenesis of perinatal hypoxic-ischemic brain injury.
abstract: BACKGROUND
  Pathogenesis of perinatal hypoxic-ischemic brain injury (HIE) is complex. In this study, we examined the role of neuroinflammation, oxidative stress and growth factors in perinatal hypoxic-ischemic brain damage.
  
  
  METHODS
  Ninety neonates (>32 weeks' gestation) with perinatal HIE were enrolled prospectively. Perinatal HIE was categorized into three stages according to the Sarnat and Sarnat clinical scoring system and changes seen on amplitude integrated electroencephalography. Cerebrospinal fluid (CSF) for interleukin-6 (IL-6) and glutathione peroxidase analysis was taken in the first 48 h of life and subsequent CSF for neuron-specific enolase (NSE) and vascular endothelial growth factor (VEGF) analysis 72 h after birth. Neurodevelopmental outcome was assessed at 12 months of corrected gestational age using the Denver Developmental Screening Test.
  
  
  RESULTS
  Concentrations of NSE in CSF correlated with severity of HIE (P < 0.0001) and corresponded well with subsequent neurodevelopmental outcome. Concentrations of IL-6 in CSF were markedly increased in neonates with severe HIE (P < 0.0001) and those with subsequent neurological sequels, but were normal in the majority of neonates with mild and moderate HIE. Glutathione peroxidase activity in CSF was significant with the stage of HIE (P < 0.0001) and gestational age (P < 0.0001) and corresponded well with subsequent neurodevelopmental outcome. Advanced stage of HIE was associated with increased concentrations of VEGF in CSF (P < 0.0001). Neurological outcomes at 12 months of age correlated best with CSF level of NSE (P < 0.001) and IL-6 (P < 0.001).
  
  
  CONCLUSIONS
  Our results suggest that neuroinflammation plays a principal role in perinatal hypoxic-ischemic brain damage and we postulate that oxidative stress and upregulation of VEGF might be important contributing factors in the pathogenesis of hypoxic-ischemic brain injury, particularly in preterm neonates.
authors.affiliation: Department of Neonatology, Institute of Gynecology and Obstetrics - Clinical Centre of Serbia, Belgrade, Serbia. bdvasilj@eunet.rs
authors.forename: Brankica
authors.initials: B
authors.lastname: Vasiljevic
authors.forename: Svjetlana
authors.initials: S
authors.lastname: Maglajlic-Djukic
authors.forename: Miroslava
authors.initials: M
authors.lastname: Gojnic
authors.forename: Sanja
authors.initials: S
authors.lastname: Stankovic
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ignjatovic
authors.forename: Dragana
authors.initials: D
authors.lastname: Lutovac
mesh_terms: D015415:Biomarkers / Q000134:cerebrospinal fluid; D002547:Cerebral Palsy / Q000209:etiology; D002658:Developmental Disabilities / Q000209:etiology; D004569:Electroencephalography; D004827:Epilepsy / Q000209:etiology; D005260:Female; D005979:Glutathione Peroxidase / Q000134:cerebrospinal fluid; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000134:cerebrospinal fluid / Q000150:complications* / Q000201:enzymology; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D008297:Male; D018384:Oxidative Stress; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid; D011446:Prospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D005979:Glutathione Peroxidase; D010751:Phosphopyruvate Hydratase