Abstracts

The mechanisms by which trauma or status epilepticus trigger epileptogenesis in some people but not in others are not clear. The development of markers to identify the changes associated with the process of epileptogenesis may provide new means for initiating earlier treatment to aid in prevention of recurrent spontaneous seizures. Here we performed a comparative analysis of changes in electrical activity recorded in multiple brain areas following status epilepticus in rats that develop or do not develop recurrent spontaneous seizures.
Under anesthesia, recording microelectrodes (tungsten, 50 um) were implanted in 6 different areas of hippocampal-entorhinal circuitry and piriform cortex. Stimulating electrodes were implanted in the right perforant path (PP), and a cannula was implanted in the right posterior hippocampus. After one week for recovery, baseline wide band electrical activity (0.1 Hz [ndash] 5kHz) and evoked responses to PP stimulation in the right dentate gyrus (DG) were recorded. Recordings were subjected to power spectral analysis (PSA) of frequency bands ranging from 0.1 to 200Hz, and brain excitability was measured during stimulation with input/output (I/O) curves. After obtaining baseline data, KA (0.2 ul/0.2ug) was injected though the cannula to produce acute status epilepticus, and the same tests were carried out at intervals during daily recordings over a period of 40 days after KA injection.
Of the 16 rats injected, 9 (56%) developed recurrent spontaneous seizures. In comparing rats with and without seizures, we found no significant relationship between severity of status epilepticus and development of epilepsy. Also, there was no consistent change in power of any frequency band of EEG activity between rats that became epileptic and those that did not. Rats that became epileptic showed a significantly steeper I/O curve of the DG response evoked by PP stimulation during the latent period following status. Interictal EEG spikes were observed bilaterally in both groups of rats. Fast Ripple (FR) oscillations were observed only in the posterior hippocampus and right entorhinal cortex unilateral to the KA lesion in the group of epileptic rats with rare seizures (3-5 per month, n=7). In rats with frequent seizures (more than 10 per mo, n=2), FR were recorded bilaterally in the hippocampus and entorhinal cortex.
Our results suggest that a predisposition to develop epilepsy after brain damage may exist for different rats. In this study, global characteristics of EEG measured with PSA did not reflect ongoing development of epileptogenesis. The increased I/O slope of the PP evoked DG response was the only significant marker of epileptogenesis in animals that developed seizures in comparison to those rats which did not. Finally, the more sites recording FR, the greater the frequency of seizures, suggesting FR are not only localizing markers but also reflect the severity of epilepsy.
[Supported by: NIH grants NS-33310 and NS-02808]