Abstracts

Perinatally acquired stroke syndromes which result in cortical lesions may lead to epileptogenic sequelae and intractable epilepsy. Structural and functional plasticity of the developing brain after a cerebro-vascular event in the fetal and neonatal periods is thought to play a major role in pathogenesis. We hypothesized that the P7 model for perinatal HI with modified Levine[rsquo]s method would induce epileptogenesis at the peri-lesional site. Spontaneous generalized tonic-clonic seizures would then occur and increase in intensity and frequency with time. To study this phenomenon we used continous video-telemetry to monitor chronic cortical EEG[rsquo]s in freely behaving rats. Sprague Dawley rat pups that had undergone a permanent unilateral ligation of the right common carotid artery at P7 followed by global hypoxia (2 h of 92% nitrogen, 8% oxygen) were implanted with 3 channel (ch) telemetry units at the age of 2 months. Bipolar subdural electrodes were implanted in the following locations: ch1 over the core of the infarct, ch2 the peri-infarct somatosensory region in the ipsilateral cortex (right hemisphere) and ch3 at coordinates corresponding to ch1 in the contralateral hemisphere. Electrode placement was based on our previously described structural organization of HI induced cortical lesion, defined by the immature nature of neonatal haemodynamics similar to the parasagittal cerebral infarcts seen in human neonates with hypoxic encephalopathy (Soc. Neurosci. Abstr 29:#211.5). Telemetric data acquisition was done with the Dataquest system and was analyzed with customized software written in Visual Basic. Analysis of the EEG data detected seizures much earlier than previously determined by a 6 h per week monitoring protocol. Episodes of purely electrographic non-convulsive seizures were documented that would be difficult to identify behaviorally. The onset of seizure activity in most cases was recorded simultaneously on all three EEG channels, but when there was evidence of lateralization, the seizures predominantly started in the ipsilateral cortex with instances of a clear initiation in the peri-lesional (penumbra) zone (ch 2). Six month old rats showed a much higher frequency of seizures compared to the 2 month old rats. Seizures often appeared in clusters with robust interictal spike activity. Seizure durations ranged from 26 sec to 136 sec with an average of 86 sec. There was a correlation between severity of the motor seizures and seizure duration. This study describes a rodent model to study the human condition of neonatal HI induced epilepsy which results in (1) both complex partial and generalized tonic-clonic seizures, and (2) evidence of increasing seizure frequency with time after the perinatal HI insult. (Supported by AHA 0410026Z and NS45144.)