Resveratrol exacerbates spike-wave discharges in genetic absence epileptic WAG/Rij rats

Resveratrol (RES), a natural supplement with reported antiepileptic effects, has not been evaluated in absence epilepsy. This study investigated the impact of RES on spike-wave discharges (SWDs) and electrocorticographic (ECoG) frequency bands in WAG/Rij rats.

Tripolar electrodes were surgically implanted onto the skulls of rats. Following a 7-day recovery period, rats received intraperitoneal injections of either DMSO/Saline: 1/9 or single doses of RES at 10, 20, or 40 mg/kg. ECoG recordings were obtained for three hours before and after the injections to assess acute effects on SWDs. To evaluate long-term effects, RES or vehicle was administered once daily for a total of seven injections. ECoG recordings were performed 24 h after the 3^rd and 7^th injections. Additionally, detailed waveform analyses were conducted for the 40 mg/kg RES group.

Long-term administration of RES at the doses of 20 and 40 mg/kg increased the number of SWDs 24 h after the 3^rd and 7^th injections, whereas it did not alter the mean duration of SWDs. Time-domain EEG analysis revealed progressive increases in amplitude variability, Hjorth activity, and spectral power following long-term RES treatment. Frequency-domain analysis showed a consistent increase in normalized power in the delta, theta, alpha, and beta bands after repeated RES injections.

Unlike the antiepileptic effects reported in other epilepsy models, the present study suggests that RES may promote network-level hyperexcitability in a genetic absence epilepsy model, and its effects on seizure activity appear to vary depending on the epilepsy subtype, dosage, and duration of administration.