Abstracts

Rationale: Temporal lobe epilepsy (TLE) often occurs after a brain insult such as status epilepticus, brain trauma or infection. Current pharmacotherapy for TLE is symptomatic, suppressing seizures but does not impact the development or progression of the disease.  Previous results from our lab have shown that treatment with sodium selenate immediately after the brain insult and before the appearance of spontaneous seizures limits the severity of the disease. However, most patients that present at the clinic are already experiencing seizures. Therefore, in this study we set out to evaluate if novel drug treatments would be able to modify the progression of epilepsy, including the frequency and severity of the seizures, behavioural comorbidities and neuroimaging changes in a chronically epileptic rats. Methods: 11-week old Wistar rats underwent kainic acid induced SE for four hours. Sham animals received saline injections only. SE was terminated with diazepam. Nine weeks after SE, animals were implanted with EEG recording electrodes and EEG was recorded continuously for four weeks. Animals were assigned to one of four treatment groups: post-SE + sodium selenate (1mg/kg/day, n=12); post-SE + levetiracetam (200mg/kg/day, n=12); post-SE + vehicle (n=11); sham + vehicle (n=13). Treatments were delivered by continuous subcutaneous infusion for four weeks. EEG recordings were acquired in the second and fourth week of treatment. Four and eight weeks after completion of treatment, the animals underwent seven days of continuous video-EEG monitoring to evaluate the disease modifying effects of the different treatments. Behavioural tests were performed to evaluate anxiety, depression, social interaction, motor, learning and memory. Brain was collected for post-mortem MRI analysis.  Results: Following drug washout, post-SE animals treated with sodium selenate had a reduced number of seizures per day when compared to vehicle. Moreover, treatment with sodium selenate and levetiracetam improved learning and memory when compared to vehicle (p> 0.05) in the Morris water maze. Conclusions: Treatment with sodium selenate has a disease modifying effect in the post-SE model of TLE, and also reduces comorbid learning and memory deficits associated with this disorder. Sodium selenate has been found to have a favourable safety facilitating the translation of into a clinical trial. Funding: THe work in this abstract has been funded by the NHMRC program grant to Prof. Terence O'Brien