Abstracts

Rationale: Rodent models of induced status epilepticus (SE) are commonly employed to understand mechanisms of epileptogenesis and to develop potential therapeutics for preventing the development of epilepsy or for decreasing seizure frequency. Outcomes measures resulting from SE include cell death, latency time to chronic seizures, and seizure frequency. There is significant variability in the impact of the SE, even when the same dose of the chemoconvulsant or type of injury is administered. To account for this variability it is desirable to develop an objective measure of the severity of SE. Here, we consider the use of several EEG measures as surrogates for the severity of SE, correlating these with resultant cell death, seizure latency and spontaneous seizure totals over time. Methods: Video-EEG was obtained from a total of 19 pilocarpine-treated animals. Twelve of the animals were used to determine potential correlations between SE surrogate measures and seizure latency correlations and 7 were used to determine cell death (Fluoro-Jade staining) correlations. Fluoro-Jade counts from CA1, CA3, and the dentate hilus of the hippocampus were averaged using 10 sections from each animal. Cortical EEG recordings were collected from both hemispheres using Pinnacle Technology systems. Sampling rates were either 200 Hz (n = 7) or 1000 Hz (n=5). Metrics used to quantify SE included: maximum power, integrated power over the 24 hour status period, relative (to baseline) integrated power, and duration of elevated EEG power. The power was also determined in the delta, theta, alpha, 15-30 Hz, 30-50 Hz, 50-70 Hz and 70-100 Hz frequency bands. Software for these calculations was written using Visual Basic subroutines. Results: Moderate strength correlations (0.3-0.4) were found at multiple frequencies between the integrated EEG power and cumulative seizure total at 1, 2 and 4 weeks following SE. Strong correlations (>0.5) were found between relative integrated power during SE and the cumulative seizure total in multiple frequency bands. Strong correlations were also noted between time with elevated EEG power and cumulative seizure total for multiple frequency bands. Moderate strength correlations were noted at multiple frequencies between time with elevated EEG power and the Flouro-Jade counts. Correlations were greatest in the CA3 and hilar regions. Conclusions: There were moderate correlations between both relative integrated power during SE, duration of elevated EEG power and cumulative seizure totals over time. Correlations were not consistently found between latency or cell counts and EEG characteristics during SE, possibly as a result of an insufficient number of animals and/or many additional factors impacting SE other than the EEG characteristics of the SE. Acknowledgements: Work was performed using support from NINDS grants 5 K08 NS053610-05 (AMW) and NIH R01 NS 051710 (ABK).