NUTRACEUTICAL COMPOUNDS TO PREVENT NEURONAL DEATH IN A MOUSE MODEL OF HUMAN TEMPORAL LOBE EPILEPSY

Temporal lobe epilepsy (TLE) is one of the most prevalent forms of epilepsy and is characterized by recurrent seizures, hippocampal neurodegeneration, and neuroinflammation. Despite available antiepileptic drugs, effective neuroprotective strategies remain limited, highlighting the need for novel therapeutic approaches. This study evaluated the neuroprotective effects of pterostilbene (PTE) administered before and after seizure induction in a mouse model of TLE. Building on the hypothesis that advanced formulations could enhance these effects, two newly synthesized cocrystal-engineered derivatives, cocrystal1 and cocrystal2, were therefore evaluated, specifically focusing their bioavailability. To these aims, kainic acid (KA), a well-stablished experimental model of excitotoxicity that mimics TLE in humans, mainly targeting the CA1 and CA3 hippocampal regions, was administrated intraperitoneally in two-month-old mice. Neuronal degeneration and microglial activation were evaluated using Fluoro-Jade B staining and Iba1 immunofluorescence, respectively. Based on these findings, the PTE concentration of each novel compound administered orally was detected in the plasma and brain tissue of adult mice via high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS). The results demonstrated that PTE prevents neurodegeneration and modulates microglial activation, even when administered two hours after seizure onset. Furthermore, the HPLC-MS analyse revealed significant differences in bioavailability among the new synthesized nutraceuticals compounds. Overall, these findings underscore the potential of PTE as a therapeutic agent and suggest that advanced pharmaceutical derivatives represent a promising strategy to optimize treatment outcomes in TLE.