title: Maturational change in the cortical response to hypoperfusion injury in the fetal sheep.
abstract: A characteristic of perinatal encephalopathies are the distinct patterns of neuronal and glial cell loss. Cerebral hypoperfusion is thought to be a major cause of these lesions. Gestational age is likely to influence outcome. This study compares the cortical electrophysiologic and histopathologic responses to hypoperfusion injury between preterm and near term fetuses. Chronically instrumented 0.65 (93-99-d, n = 9) and 0.9 (119-133-d, n = 6) gestation fetal sheep underwent 30 min of cerebral hypoperfusion injury. The parasagittal cortical EEG and impedance (measure of cytotoxic edema) responses plus histologic outcome (3 d) were compared. The acute rise in impedance was similar in amplitude, but the onset was delayed (5.0 +/- 0.7 versus 9.1 +/- 1.1 min, p < 0.05) in the preterm fetuses relative to those near term. In contrast the extent of the secondary rise was reduced (p < 0.01) and peaked earlier in the preterm fetuses (19.8 +/- 1.0 versus 40.5 +/- 3.5 h, p < 0.01). Both groups had a similar fall in EEG spectral edge frequency. The preterm fetuses had a milder loss of EEG intensity at 72 h (-7.7 +/- 1.5 versus -12.8 +/- 0.9 dB, p < 0.05). At both ages there was a predominantly parasagittal cortical distribution of damage with a similar pattern of neuronal loss in the thalamus and striatum. There was extensive selective neuronal loss within the upper layers of the cortex in those near term. In contrast the preterm fetuses developed subcortical infarcts (p < 0.05). The cortical response to injury altered during the last trimester. The results suggest the severity of the delayed phase of cortical neuronal injury and selective neuronal loss increased near term. In contrast, the preterm fetuses had a more rapidly evolving injury leading to necrosis of the subcortical white matter.
authors.affiliation: Research Centre for Developmental Medicine and Biology, Department of Paediatrics, University of Auckland, New Zealand.
authors.forename: K
authors.initials: K
authors.lastname: Reddy
authors.forename: C
authors.initials: C
authors.lastname: Mallard
authors.forename: J
authors.initials: J
authors.lastname: Guan
authors.forename: K
authors.initials: K
authors.lastname: Marks
authors.forename: L
authors.initials: L
authors.lastname: Bennet
authors.forename: M
authors.initials: M
authors.lastname: Gunning
authors.forename: A
authors.initials: A
authors.lastname: Gunn
authors.forename: P
authors.initials: P
authors.lastname: Gluckman
authors.forename: C
authors.initials: C
authors.lastname: Williams
mesh_terms: D000818:Animals; D001925:Brain Damage, Chronic / Q000196:embryology* / Q000209:etiology / Q000473:pathology; D001929:Brain Edema / Q000196:embryology / Q000473:pathology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000196:embryology / Q000473:pathology / Q000503:physiopathology*; D003342:Corpus Striatum / Q000196:embryology / Q000473:pathology / Q000503:physiopathology; D004569:Electroencephalography; D004594:Electrophysiology; D005333:Fetus; D005865:Gestational Age; D002546:Ischemic Attack, Transient / Q000196:embryology / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000473:pathology / Q000502:physiology; D012756:Sheep; D013788:Thalamus / Q000196:embryology / Q000473:pathology / Q000503:physiopathology