title: Delayed seizures occurring with hypoxic-ischemic encephalopathy in the fetal sheep.
abstract: The pathogenesis of perinatal hypoxic-ischemic encephalopathy is poorly understood. Most insults are thought to occur before or during birth. We have investigated the evolution of parasagittal EEG activity and distribution of neuronal damage after cerebral ischemia in chronically instrumented fetal sheep (119-126 d gestation). The vertebral-carotid anastomoses were ligated and cerebral ischemia was induced by inflating occluder cuffs around the carotid arteries for 30 min. Parietal cortical EEG activity was analyzed with real-time spectral analysis with reference to control fetuses. After ischemia, EEG activity was suppressed, then rapidly increased in intensity at 8 +/- 1 h to a peak at 9 +/- 1 h postischemia. There was increased intensity of the lower frequencies (1-7 Hz) apparent as epileptiform activity with convulsions. This low-frequency hyperactivity gradually resolved by 28 +/- 7 h postinsult. After 72 h, the loss of intensity at all frequencies and laminar necrosis of the underlying parasagittal cortex indicated irreversible brain injury. Ranking the structures in order of decreasing amounts of damage: parasagittal cortex greater than hippocampal CA1, 2, and 3 regions greater than lateral cortex, hippocampal CA4 region and striatum greater than amygdala, dentate gyrus, thalamus, and cerebellum. The evolution of EEG activity and the distribution of damage after cerebral ischemia closely resembles the time course and pathology of hypoxic-ischemic encephalopathy seen in some severely asphyxiated term neonates. The consistent electrophysiologic and histologic outcome should allow this experimental approach to be valuable in testing a number of current hypotheses relating to perinatal asphyxial encephalopathy.
authors.affiliation: Department of Paediatrics and Pathology, University of Auckland, New Zealand.
authors.forename: C E
authors.initials: CE
authors.lastname: Williams
authors.forename: A J
authors.initials: AJ
authors.lastname: Gunn
authors.forename: B
authors.initials: B
authors.lastname: Synek
authors.forename: P D
authors.initials: PD
authors.lastname: Gluckman
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000473:pathology; D004569:Electroencephalography; D005311:Fetal Hypoxia / Q000150:complications* / Q000503:physiopathology; D012640:Seizures / Q000209:etiology* / Q000503:physiopathology; D012756:Sheep; D013997:Time Factors