Efeito do surfactante Solutol® HS15 em modelo experimental de epilepsia do lobo temporal mesial

Abstract

Epilepsy is a neurological disorder characterized by a chronic predisposition of the brain oVto generate spontaneous recurrent seizures. Mesial Temporal Lobe Epilepsy (MTLE) is the most common form in adults and often resistant to available treatments. Therefore, finding new therapeutic options is urgent. Previous studies by our research group have indicated that Solutol® HS 15 (SOL), a pharmaceutical excipient used as a surfactant and drug carrier, could have anticonvulsant and antiepileptogenic action. In this study, we investigated this possibility using an animal model of pilocapine-induced status epilepticus (SE). Thus, the objective was to evaluate if SOL: i. reduces epileptic seizures during SE and in the chronic phase of epileptogenesis, ii. reduces neurodegeneration process, and iii. modulates the expression of genes associated with epileptogenesis. Male Wistar rats were pre-treated with SOL (experimental groups) or saline solution (SAL) (control groups) by intrahippocampal (I.H.) or intraperitoneal (I.P.) administration and then submitted to 90 minutes of SE. After 24 hours of SE, the animals were euthanized for histological and molecular analyses. In the chronic phase, epileptic animals received SOL or SAL treatment intraperitoneally for 15 days. All animals were monitored by video during SE, latency, and chronic phase, and their seizures were evaluated using the Racine scale. Total hippocampal neurodegeneration and in its sub-regions (Cornu Ammonis: CA1 and CA3; and hilus) were evaluated with Fluoro-Jade. The expression of transcripts associated with epileptogenesis was measured by RT-qPCR. Statistical analysis was performed using GraphPad Prism 9.0 software. Thus, pre-treatment with SOL reduced the total number of seizures during SE by 38.97% (via I.H.) and 60.87% (via I.P.), total hippocampal neurodegeneration (29.07% to 66.62%) in all tested models. Furthermore, animals pretreated with SOL had an increase and decrease in the expression of BDNF (via I.H.) and GFAP (via I.P.), respectively, indicating a neuroprotective effect. Taken together, our study showed that SOL has anticonvulsant effects during the acute and chronic phases of epileptogenesis, as well as reduces hippocampal neurodegeneration and modulates the expression of BDNF and GFAP. These findings are promising for the potential role of SOL in epilepsy treatment.