Outcome after ischemia in the developing sheep brain: an electroencephalographic and histological study

Abstract

The role of seizures occurring with perinatal hypoxic-ischemic encephalopathies is unclear. We examined the relationships between the time course of parasagittal electroencephalographic (EEG) activity and pathological outcome following transient cerebral ischemia, which was induced in 33 chronically instrumented fetal sheep by occluding the carotid arteries after ligation of the vertebral-carotid anastomoses. The EEG was quantified with real-time spectral analysis. Histological outcome was assessed 72 hours later. After 10 or 20 minutes of ischemia, EEG activity was depressed and then progressively recovered and mild selective neuronal loss was seen. The length of this depression correlated with the duration of ischemia (r = 0.88). After 30 or 40 minutes of ischemia, EEG activity remained depressed for 8 +/- 2 hours, followed by a rapid transition to low-frequency epileptiform activity that reached maximum intensity at 10 +/- 3 hours. By 72 hours, EEG intensity had fallen below control levels. This sequence of prolonged depression, epileptiform activity, and then loss of intensity was associated with the development of laminar necrosis of the underlying cortex. These electrophysiological sequelae may have prognostic value. The results indicate that after a severe hypoxic-ischemic insult, the parasagittal cortex becomes hyperexcitable before the final loss of activity. Secondary neuronal death may occur in this phase.