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

Journal: Brain Research
Published:
Abstract

Background: Development 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.

Authors
Camilo Ríos, Iñigo Aguirre Aranda, Arturo Avendaño Estrada, Miguel Ángel Ávila Rodríguez, Joaquín Manjarrez Marmolejo, Javier Franco Pérez, Marcela Islas Cortez, Amairani Ruiz Diaz, Marisela Méndez Armenta, Araceli Diaz Ruiz