Characterization of the anticonvulsant effect of dapsone on metabolic activity assessed by [18F]FDG -PET after kainic acid-induced status epilepticus in rats

Abstract

BackgroundDevelopment of effective drugs for epilepsy are needed, as nearly 30 % of epileptic patients, are resistant to current treatments. This study is aimed to characterize the anticonvulsant effect of dapsone (DDS), in the kainic acid (KA)-induced Status Epilepticus (SE) by recording the brain metabolic activity with an [18F]FDG-PET analysis. Methods: Wistar rats received KA (10 mg/kg, i.p., single dose) to produce sustained seizures. [18F]FDG-PET and electroencephalographic (EEG) studies were then performed. DDS or vehicle were administered 30 min before KA. [18F]FDG uptake and EEG were evaluated at baseline, 2 and 25 h after KA injection. Likewise, caspase-8, 3 hippocampal activities and Fluoro-Jade B neuronal degeneration and Hematoxylin-eosin staining were measured 25 h after KA. Results: PET data evaluated at 2 h showed hyper-uptake of [18F]FDG in the control group, which was decreased by DDS. At 25 h, hypo-uptake was observed in the control group and higher values due to DDS effect. EEG spectral power was increased 2 h after KA administration in the control group during the generalized tonic-clonic seizures, which was reversed by DDS, correlated with [18F]FDG-PET uptake changes. The values of caspases-8 activity decreased 48 and 43 % vs control group in the groups treated with DDS (12.5 y 25 mg/kg respectively), likewise; caspase-3 activity diminished by 57 and 53 %. Fewer degenerated neurons were observed due to DDS treatments. Conclusions: This study pinpoints the anticonvulsant therapeutic potential of DDS. Given its safety and effectiveness, DDS may be a viable alternative for patients with drug-resistant epilepsy.