Abstracts

Rationale: Status epilepticus (SE) is a dynamic state. There are progressive changes in clinical behavior, response to treatment, extent of neuronal damage, and EEG pattern during prolonged clinical and experimental SE. Status epilepticus also causes deficits in learning and memory, but progressive impairment with increasing severity of SE has been little studied. We tested the hypothesis that the EEG stage during kainic acid-induced SE predicts the extent of subsequent cognitive impairment.Methods: Forty-eight 250-280 gm male Sprague-Dawley rats were implanted with 4 stainless steel epidural electrodes for EEG recording. Status epilepticus was induced by 15 mg/kg IP injection of kainic acid. EEG was continuously recorded before and after injection, and SE was stopped at EEG stage I (discrete seizures), III (continuous ictal activity), IV (continuous ictal activity punctuated by flat periods), or V (periodic epileptiform discharges) (Treiman et al., Epilepsy Res 5:49-60, 1990) with IP diazepam (10 mg/kg) plus phenobarbital (25 mg/kg). Control rats were given PB vehicle and did not develop SE. Spatial learning and memory were assessed one week prior to SE induction (baseline) and one week after SE using a modification of the Morris Water Maze (J Neurosci Methods 1984; 11: 47-60). Learning impairment was tested in six trials on each of four sequential days. Effect of the SE EEG stage on the mean escape time to a submerged platform was compared. The mean escape time for the six trials on test day 4 of week 1 (pre-SE) was compared with the mean of the six trials on test day 1 of week 2 (post-SE) to assess the effect of SE on spatial memory.Results: There were no significant differences between any of the groups in pre-SE water maze performance. However, post-SE day 1 mean escape times were significantly worse compared with pre-SE day 4 (test of memory) as well as the mean escape times for all test days (test of learning) in Stage IV and Stage V rats when compared to controls, Stage I, and Stage III rats (p<0.001). No significant differences were found between control, Stage I and Stage III rats, or between Stage IV and Stage V rats.Conclusions: Status epilepticus results in a marked impairment of both visual-spatial memory and learning. The later the EEG stage, the greater the impairment. Thus progressive cognitive impairment, in addition to other dynamic changes cited above, is also an effect of prolonged SE. These data provide further evidence that the EEG stage during prolonged SE is a marker of its severity. Study supported by the Barrow Neurological Foundation