Abstracts

It has been hypothesized that the severity of brain injury at the time of the initiating incident determines - or at least affects - the progression of epileptogenesis. We hypothesized that the severity of convulsive status epilepticus during kainate treatment is positively related to the time to the first electrographic seizure and to the amount of Timm stain in the inner molecular layer of the dentate gyrus. Eight rats were implanted with electroencephalographic radiotelemetry monitors, and both electrographic and behavioral data were recorded continuously for the next 120-150 days. One week after the surgery, five rats were treated with kainic acid (5 mg/kg, IP) until each rat experienced convulsive status epilepticus. Motor seizures were observed during the 24-h period after the initial kainate injection. Seizures were quantified based on the number of motor seizures, the duration of individual motor seizures, and seizure type (Racine,1972[italic] Electroenceph Clin Neurophysiol,[/italic] 32:281). The animals were then ranked by the total duration of seizures (i.e., total number of seizures x the mean seizure duration) and by a scaling of the seizure type (i.e., type 3=1, type 4=2, type 5=3; followed by summation of the total of the seizure types); these two indices were then summed, resulting in an overall seizure score. At the end of the 120-150 day recording period, the animals were euthanized and processed for Timm staining, which was graded using the Tauck and Nadler scale (1985, [italic]J. Neurosci[/italic], 5:106) by an observer blind to the animals[rsquo] treatment. The total number of seizures observed during the 24 h following kainate treatment ranged from 59-123 seizures per rat, and the mean seizure duration was 48 [plusmn] 6 sec. The mean number of days to the first observed electrographic seizure was 12 [plusmn] 10 days. Mean Timm stain scores ranged from 1.00 to 2.42. There was a positive correlation between the seizure score derived during treatment and the time to the first electrographic seizure (r²=0.79, p=0.04), and a positive correlation between the seizure score and Timm stain in the inner molecular layer of the dentate gyrus (r²=0.84, p=0.02). Timm stain in the inner molecular layer was also positively correlated with the time to the first electrographic seizure (r²=0.93, p=0.008). These results suggest a strong association between the severity of the convulsive seizures during kainate treatment and the progression of epileptogenesis. The data suggest that it may be possible to predict the rate of seizure progression in groups of animals, based on the motor seizure response during chemoconvulsant-induced status epilepticus. (Supported by NS 45144 and NS 034360)