EFFECT OF THE PHARMACEUTICAL EXCIPIENT SOLUTOL® HS 15 IN AN ANIMAL MODEL OF MESIAL TEMPORAL LOBE EPILEPSY
Epilepsy, Solutol, Neuroprotection, Anticonvulsant.
Introduction: Epilepsy is a neurological disorder characterized by a chronic predisposition of the brain to generate recurrent and spontaneous epileptic seizures (SEs). 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 from our research group have shown that Solutol® HS 15 (SOL), a pharmaceutical excipient used to carry drugs, may have anticonvulsant and antiepileptogenic effects. In this study, we investigated this possibility using an animal model of Pilocarpine-induced Status Epilepticus. Objective: To evaluate whether SOL affects Status Epilepticus (SE) and the chronic phase of epileptogenesis. Methodology: To analyze the acute phase of epileptogenesis, male Wistar rats were pretreated with SOL (experimental groups) or saline solution (SAL) (control groups) via intrahippocampal (I.H.) or intraperitoneal (I.P.) administration, and then subjected to 90 minutes of SE. They were euthanized 24 hours after SE reversal for histological and molecular analyses. In the chronic phase, epileptic animals received treatment with SOL or SAL via intraperitoneal route for 15 days. All animals were video-monitored during SE, latency, and chronic phase, and their seizures were evaluated using the Racine scale. Total hippocampal neurodegeneration and in its subregions (Ammon's Horn: CA1 and CA3; and Hilus) were assessed with Fluoro-Jade. The expression of transcripts associated with epileptogenesis was measured by RT-qPCR. Statistical analysis was performed using GraphPad, Prism 9.0. Results: Pretreatment with SOL reduced the total number of seizures during SE by 29.94% (via I.H.) and 33.93% (via I.P.). It also reduced hippocampal neurodegeneration by 25.02% to 43.43% in all tested models. Additionally, animals pretreated with SOL showed increased expression of BDNF (via I.H.) and decreased expression of GFAP (via I.P.), indicating a neuroprotective effect. In the chronic phase, treatment with SOL had an anticonvulsant effect in 70% of the animals. Conclusion: The study demonstrates that SOL has anticonvulsant effects during SE and in the chronic phase of epileptogenesis, as well as reducing hippocampal neurodegeneration and altering the expression of BDNF and GFAP. These findings are promising for the potential role of SOL in epilepsy treatment, but further studies are needed to better understand these mechanisms