Abstracts

RATIONALE: We examined the evolution of chronic epilepsy after self-sustaining status epilepticus (SSSE) in rats. METHODS: SSSE was induced in awake adult Wistar rats by 30 min intermittent perforant path stimulation. During and after SSSE, EEG was recorded using the Harmony software (Stellate Systems) configured for automatic seizure detection, and synchronized with video monitoring. Recording electrodes were implanted bilaterally into the dorsal and ventral hippocampi,piriform and entorhinal (EC) cortices. Timm staining was examined at different time after SSSE. RESULTS: Starting one day after SSSE fast ripples (200-500 Hz, 0.5-1 s, 200-800 mV) were recorded from ipsi and contralateral EC. Those were not accompanied by behavioral components. The 1st EEG/behavioral spontaneous seizure (SS) occurred 28 2 days after SSSE (defined as day 1 for each rat). In 71% of the animals the 1st SS was stage 1 (motor arrest, facial clonus).In the other animals 1st SS was stage 4-5 (rearing/rearing and falling)limbic seizure. Seizure count on day 1 was 6 1 (range 1-18) and did not change significantly with time (7.8 1.3 on day 10; 6.6 1 on day 30). After 14 3 of stage 1-2 SS, all rats progressed to stage 4-5. 3 out of 12 of those animals showed total switch to stage 4-5 SS, while 9 rats alternated stage 1-2 and stage 4-5. During interictal periods, rats showed frequent (up to 5/min) episodes of fast ripples in the ventral hippocampi and/or EC. Each SS was preceded by synchronous fast ripples in right and left ventral hippocampi. All examined animals showed mossy fiber sprouting in the dentate gyrus, evident as early as 20 days after PPS even in rats with no seizures, and reaching maximal values by 12 weeks after SSSE. CONCLUSIONS: 1. EEG changes appear on the first day after SSSE and persist throughout the course of chronic epilepsy. 2. First SS occurs 3-4 weeks after SSSE. 3. While there is no progression in terms of SS frequency, there is one in terms of seizure severity in the animals with initial stage 1 seizures. 4. Mossy fiber sprouting increases with the course of chronic epilepsy, but does not correlate with the incidence of SS. Supported by NIH grants NS13515, NS08208, NS33310, NS01792 and VA Research Service.