Abstracts

Rationale: Neonatal cerebral stroke accounts for 10-15% of the total number of neonates with seizures, and is the main identified cause of congenital hemiplegia (Anderson et al., 2008). We studied the effect of phenobarbital on the quantity of seizures, and the size of the lesion.Methods: P7 (7 day-old) rats were subjected to ischemia-reperfusion (Renolleau et al., 1998), which received either phenobarbital (10, 20, and/or 40 mg/kg) before and/or 3 hours after ischemia or PBS. EEG recordings were acquired and seizures were quantified by using cortical bipolar electrode on the dura, and the animals will be connected to an MP100/EEG100B acquisition system (BIOPAC). EEG will be acquired using AcqKnowledge 4.1 software along with simultaneous digital video. Two investigators blind to the treatment group determined the number of seizures, the size of the lesion (24 hours after ischemia), and cell death measured with the TUNEL assay.Results: During the 50 min of ischemia, the first change is a modification of the background with a low voltage activity after carotid occlusion observed in all animals. Two types of epileptic events (EEG recording) are observed during ischemia and reperfusion. The first epileptic event occurred within the first 30 minutes of the ischemic phase, and consists of burst of spikes of high amplitude occurring at regular interval with a return to a normal background between 2 discharges. During the discharges, myoclonic jerks, vocalization, head bobbing, and repetitive clonic jerks can be observed. The second type of epileptic event (only observed during reperfusion) is seizure of longer duration consisting in organized discharge of spikes/spikes waves of progressive amplitudes à 1-2 Hz associated with clonic movements of lower amplitude. In contrast, all animals exhibited epileptic “bursts” consisting in high voltage spikes and slow waves as early as re-flow occurred, and eighty percent of them displayed seizures beginning at 7.8±8.5 hours of EEG monitoring. Phenobarbital, whatever the dose and timing administration used did not reduce the lesion size (15.1±4.8 vs 12.1±2.6, NS), and the number of TUNEL-positive nuclei in the cortex (154.9±30.7 vs 148.3±45.9, NS). At a dose of 20 mg/kg given before ischemia, phenobarbital delay the time of their first occurrence 15.8±8.4 hours (p<0.05 vs ischemia-PBS) and ignificantly reduced the duration of epileptic “bursts” (525±633 vs 1744±864 s, p=0.0012) but did not significantly reduce the number and duration of seizures.Conclusions: Our data demonstrate the occurrence of seizure in the acute phase of neonatal stroke. Despite a reduction of one of the two components of the recorded epileptic events, Phenobarbital is not the best pharmacological drug to treat both neonatal seizures in case of neontatal stroke. Moreover, phenobabital doesn't change the volume of the infarct . Our ischemic model in the P7 rat pups, with EEG profiles similar to those observed in most of infants with cerebral infarction, may represent a relevant model to further evaluate the relationship between the acute seizure and the volume of neonatal stroke.