Time course of intracellular edema and epileptiform activity following prenatal cerebral ischemia in sheep.

The role of edema in the pathogenesis of hypoxic-ischemic injury in the immature brain is controversial. We studied 15 chronically instrumented fetal sheep following transient cerebral ischemia, to estimate changes in extracellular space using an impedance technique, to quantify the electroencephalogram with real-time spectral analysis, and to assess histologic outcome 3 days after the insult. These measurements were made in the parasagittal cortex. There was a rapid loss of extracellular space from 5 +/- 2 minutes after the onset of ischemia. Following 10 minutes of ischemia (n = 7) the intracellular edema peaked but then quickly resolved (6 +/- 4 minutes), and mild selective neuronal loss was seen. In contrast, the swelling was biphasic after 30-40 minutes of ischemia (n = 8). The early edema resolved slowly (28 +/- 12 minutes) but incompletely, and secondary swelling began at 7 +/- 2 hours and peaked at 28 +/- 6 hours. The early swelling was the more severe. Postinsult epileptiform activity began at 8 +/- 2 hours and peaked at 10 +/- 3 hours; later there was laminar necrosis of the underlying cortex. The secondary decrease of extracellular space indicates that a progressive loss of membrane function started with the onset of postischemic epileptiform activity. The increased metabolic load of the epileptiform activity may have worsened this delayed deterioration.