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.