Low-dose 7,8-Dihydroxyflavone Administration After Status Epilepticus Prevents Epilepsy Development
We found that low (5 mg/kg), but not high-dose 7,8-DHF (10 mg/kg) can exert strong anti-epileptogenic effects in the lithium-pilocarpine model (i.e., highly significant reduction in the frequency of spontaneous seizures and in the time to first seizure after status epilepticus). The mechanism of these different dose-related effects remains to be elucidated
The lower dose of 7,8-DHF almost completely prevented the occurrence of SRSs in the observation period of 21 days. Whereas, as noted above, 14 of 17 vehicle-treated rats displayed spontaneous motor seizures, only 2 of 18 rats treated with 5 mg/kg 7,8-DHF experienced each a single motor seizure, and this happened much later than in the vehicle group, i.e., 18 and 20 days after SE
7,8-DHF may represent a candidate for a preventive, anti-epileptogenic therapy or, probably more realistically, a template for developing an effective and well-tolerated anti-epileptogenic drug. In the prospect of clinical translation of 7,8-DHF, the present data suggest that an accurate dose titration would be needed, and this may imply identification of an optimal window of plasma concentrations and a better understanding of the mechanism of 7,8-DHF bell-shaped anti-epileptogenic effect.
