Continuous Electroencephalographic Monitoring with Radio-Telemetry in a Rat Model of Perinatal Hypoxia–Ischemia Reveals Progressive Post-Stroke Epilepsy

摘要

The development of acquired epilepsy after a perinatal hypoxic–ischemic (HI) insult was investigated in rats. After unilateral carotid ligation with hypoxia on postnatal day 7, cortical electroencephalographic and behavioral seizures were recorded with continuous radio-telemetry and video. Chronic recordings were obtained between 2 and 12 months of age in freely behaving HI-treated and sham control rats. The hypotheses were that the acquired epilepsy is directly associated with an ischemic infarct (i.e., no lesion, no epilepsy), and the resultant epilepsy is temporally progressive. Every HI-treated rat with a cerebral infarct developed spontaneous epileptiform discharges and recurrent seizures (100%); in contrast, no spontaneous epileptiform discharges or seizures were detected with continuous monitoring in the HI-treated rats without infarcts. The initial seizures at 2 months generally showed focal onset and were nonconvulsive. Subsequent seizures had focal onsets that propagated to the homotopic contralateral cortex and were nonconvulsive or partial; later seizures often appeared to have bilateral onset and were convulsive. Spontaneous epileptiform discharges were initially lateralized to ipsilateral neocortex but became bilateral over time. The severity and frequency of the spontaneous behavioral and electrographic seizures progressively increased over time. In every epileptic rat, seizures occurred in distinct clusters with seizure-free periods as long as a few weeks. The progressive increase in seizure frequency over time was associated with increases in cluster frequency and seizures within each cluster. Thus, prolonged, continuous seizure monitoring directly demonstrated that the acquired epilepsy after perinatal HI was progressive with seizure clusters and was consistently associated with a cerebral infarct.