Behavioral characteristic as a biomarker of development and phenotype of epilepsy in the temporal lobe epilepsy induced by electrical stimulation of the amygdala in rats

INTRODUCTION: Non-invasive biomarkers of epileptogenesis and epilepsy in experimental models would allow fast and easy evaluation of disease development and impact of treatments aiming at modification of disease development or progress. AIM(S): The project was conducted to test the hypothesis that there are differences in the results of behavioral tests depending on 1) the time to develop epilepsy, measured by the length of the latency to the first spontaneous seizure, and 2) the intensity of epilepsy, measured by the number of seizures. METHOD(S): Animals were kept in enriched environment and were subjected to the handling procedure. Epilepsy was induced by status epilepticus using electrical stimulation of the amygdala (25 min, 100-ms train of 1-ms biphasic square‑wave pluses, 400 µA, 60 Hz, delivered every 0.5 s). EEG was used to classify rats into animals groups with short (<20 days, n=7) and long (>20 days, n=8) latency and into groups with low (SE_L: 62±64.5, n=7) and high (SE_H: 456±185, n=8) seizure number. We applied following behavioral tests: behavioral hyperexcitability, open field, novel object exploration, elevated plus maze and Morris water maze. RESULTS: We observed decreased learning abilities of epileptic animals compared to control (SE: 14.07±9.5, CTRL: 28.36±21.5, p<0.001) in 4 training day of Morris water maze. We observed no difference in the stress level, activity and learning between groups with short and long latency in all behavioral tests and between groups with low and high seizures number. However, we observed increased stress level, measured by number of imputes to the closed arms, in group with high number of seizures in elevated plus maze carried out in 26 week compared to animals with low seizures number (SE_H: 35±13.6, SE_L: 15.14±8.9, p<0.01). CONCLUSIONS: Increased stress level in elevated plus maze might become convenient biomarker of epilepsy phenotype. FINANCIAL SUPPORT: This work was supported by the FP7-HEALTH project 602102 (EPITARGET) and Polish Ministry of Science and Education grant W19/7.PR/2014.