title: Validation of a neuropathology score using quantitative methods to evaluate brain injury in a pig model of hypoxia ischaemia.
abstract: BACKGROUND
  Neuropathological examination is the classic outcome measure in experimental studies of newborn brain injury to evaluate novel therapies. We have used a graded neuropathology score in an established global model of perinatal hypoxic-ischaemic (HI) injury. We wished to validate the score using cell counting in our model.
  
  
  METHODS
  32 newborn pigs underwent a 45 min global HI insult then maintained at normothermia (NT, rectal temperature, Trectal 38.5 °C) for 72 h or mild total body hypothermia (HT, Trectal 37.0 °C) combined with selective head cooling for 48 h and subsequently maintained at NT for 24h before brain perfusion fixation. A perinatal pathologist scored haematoxylin and eosin stained 6 μm histological sections for injury in the hippocampus and basal ganglia on a 9-step scale (0.0=no injury, 4.0=>75% injury). We counted the number of healthy neurons in the hippocampus CA1 region and putamen using morphological criteria in eight random, non-overlapping fields from representative sections.
  
  
  RESULTS
  Healthy neuronal cell density correlated with neuropathology score in the hippocampus CA1 (r = -0.74) and in the putamen (r = -0.75) and both measures detected a difference between groups. The correlation coefficients were better for the NT compared to the HT group in both the hippocampus (r = -0.87 vs. -0.53) and putamen (r = -0.77 vs. -0.54).
  
  
  CONCLUSIONS
  We have validated a histological neuropathological scoring system in our model of perinatal HI by showing correlation between neuronal cell count and estimated injury.
  
  
  CONCLUSIONS
  Our neuropathology score is a valid method to assess brain injury with good reproducibility and sensitivity.
authors.affiliation: Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, St Michael's Hospital, Southwell Street, Bristol, Avon BS2 8EG, United Kingdom.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Hoque
authors.affiliation: Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, St Michael's Hospital, Southwell Street, Bristol, Avon BS2 8EG, United Kingdom.
authors.forename: Hemmen
authors.initials: H
authors.lastname: Sabir
authors.affiliation: Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, St Michael's Hospital, Southwell Street, Bristol, Avon BS2 8EG, United Kingdom; Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Postboks 1103, Blindern, 0317 Oslo, Norway.
authors.forename: Elke
authors.initials: E
authors.lastname: Maes
authors.affiliation: Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, St Michael's Hospital, Southwell Street, Bristol, Avon BS2 8EG, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bishop
authors.affiliation: Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, St Michael's Hospital, Southwell Street, Bristol, Avon BS2 8EG, United Kingdom; Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Postboks 1103, Blindern, 0317 Oslo, Norway. Electronic address: marianne.thoresen@bristol.ac.uk.
authors.forename: Marianne
authors.initials: M
authors.lastname: Thoresen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001831:Body Temperature; D001921:Brain / Q000473:pathology*; D056547:CA1 Region, Hippocampal / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000175:diagnosis* / Q000473:pathology* / Q000628:therapy; D009474:Neurons / Q000473:pathology*; D010784:Photomicrography; D011699:Putamen / Q000473:pathology; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D034421:Sus scrofa
keywords: Asphyxia; Hypothermia; Hypoxia ischaemia; Neuropathology score; Newborn