title: Role of the cerebrovascular and metabolic responses in the delayed phases of injury after transient cerebral ischemia in fetal sheep.
abstract: OBJECTIVE
  Perinatal hypoxic-ischemic injuries can trigger a cascade of events leading to delayed deterioration and cell death several hours later. The objective of this study was to characterize the cerebral blood flow responses and the changes in extracellular glucose and lactate during the delayed phases of injury and to determine their relationships with the pathophysiological events after hypoxic-ischemic injury.
  
  
  METHODS
  Two groups of near-term chronically instrumented fetal sheep were subjected to 30 minutes of cerebral hypoperfusion. In the first group, regional cerebral blood flow was measured over the next 24 hours with radiolabeled microspheres. In the second, cortical extracellular glucose and lactate were measured by microdialysis. Parietal electrocorticographic activity and cortical impedance were recorded continuously in both groups, and the extent of neuronal loss was determined histologically at 72 hours after injury.
  
  
  RESULTS
  Cerebral blood flow was transiently impaired in the cortex during reperfusion, whereas during the delayed phase, there was a marked increase in cerebral blood flow. The severity of cortical neuronal loss was related to the degree of hypoperfusion in the immediate reperfusion period and inversely related to the magnitude of the delayed hyperperfusion. Cortical extracellular lactate was elevated after injury, and both glucose and lactate secondarily increased during the delayed phase of injury.
  
  
  CONCLUSIONS
  The delayed phase is accompanied by a period of hyperperfusion that may protect marginally viable tissue.
authors.affiliation: Research Centre for Developmental Medicine and Biology, School of Medicine, University of Auckland, New Zealand.
authors.forename: R A
authors.initials: RA
authors.lastname: Raad
authors.forename: W K
authors.initials: WK
authors.lastname: Tan
authors.forename: L
authors.initials: L
authors.lastname: Bennet
authors.forename: A J
authors.initials: AJ
authors.lastname: Gunn
authors.forename: S L
authors.initials: SL
authors.lastname: Davis
authors.forename: P D
authors.initials: PD
authors.lastname: Gluckman
authors.forename: B M
authors.initials: BM
authors.lastname: Johnston
authors.forename: C E
authors.initials: CE
authors.lastname: Williams
mesh_terms: D000818:Animals; D016923:Cell Death; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation; D005333:Fetus; D005947:Glucose / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D019344:Lactic Acid / Q000378:metabolism*; D017551:Microdialysis; D015424:Reperfusion; D012756:Sheep; D013997:Time Factors
chemical_list: D019344:Lactic Acid; D005947:Glucose