Blood brain barrier dynamics and antiepileptogenic effects of antiepileptic drug- bound nanoparticle in WAG/Rij rats as a genetic absence epilepsy model

Epilepsy is a neurological disease that affects more than 65 million people worldwide. Absence epilepsy is seen in children and adolescents. The blood-brain barrier (BBB) constituted by the endothelial cells of the brain microvessels limits the passage of circulatory substances into the brain parenchyma. In this study, adult WAG/ Rij rats were used to show the effects on seizures of lacosamide (LCM) associated with gold nanoparticle (GNP). To see the long-term effects of GNP on seizures, EEG recordings were obtained by electrodes placed in the right and left hippocampus, and an Elevated Plus Maze (EPM) test was performed. The presence of GNPs in the brain was determined by using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and electron microscopy. At the same time, hemogram analysis of the animals were performed at the end of the experiments. Application of LCM with or without GNP caused significant decreases in amplitude, and seizure frequency values compared to baseline values (p<0.01). GNP+LCM injections significantly decreased anxiety levels as well (p<0.01). The findings obtained from IVIS showed that LCM reached higher levels of brain parenchyma in the presence of GNP (p<0.01). In ultrastructural examinations, GNPs were found in the neuronal structures after passing BBB endothelial cells. There were no significant changes in hemogram values. Our results suggest that GNP is an effective transfer agent in terms of antiepileptogenic efficacy in the passage of LCM through the BBB, and more importantly, the application of low dose LCM as GNP+LCM strongly influences the amplitude, and frequency of seizures.