Suppression of postischemic epileptiform activity with MK-801 improves neural outcome in fetal sheep.
To determine the effect of suppression of epileptiform activity that develops after hypoxic-ischemic injury in the immature brain, chronically instrumented near-term fetal sheep (119-133 days) were subjected to 30 minutes of complete cerebral ischemia: 6 were given a 0.3-mg/kg bolus of MK-801 at 6 hours after the insult followed by continuous infusion of 1 mg/kg over the next 36 hours, and were compared to 6 control sheep. Electrocorticographic activity and edema within the parasagittal region of the cortex were quantified with real-time spectral analysis and impedance measurements, respectively. Histological outcome was assessed 72 hours later. The intense epileptiform activity seen from 9 +/- 2 to 30 +/- 3 hours in the control group was completely suppressed in the MK-801-treated group. The onset of secondary cortical edema was delayed from 9.4 +/- 1.1 hours to 14.8 +/- 0.7 hours (p < 0.01). Neuronal damage was reduced, particularly in the lateral cortex and hippocampus (p < 0.05). Infarction of the parasagittal cortex was not prevented. These results suggest that N-methyl-D-aspartate-mediated epileptiform activity that develops after a global hypoxic-ischemic insult worsens neuronal outcome in the immature brain.
Tan
W K
WK
Department of Pediatrics, University of Auckland, New Zealand.
Williams
C E
CE
Gunn
A J
AJ
Mallard
C E
CE
Gluckman
P D
PD
D000818:Animals; D002545:Brain Ischemia / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology; D016923:Cell Death; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D017097:Electric Impedance; D004569:Electroencephalography; D004827:Epilepsy / Q000209:etiology / Q000517:prevention & control*; D005315:Fetal Diseases / Q000209:etiology / Q000517:prevention & control*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D012756:Sheep
D016291:Dizocilpine Maleate