Naringenin-Loaded PCL Nanoparticles Attenuate Glial Activation and TNF-α Expression in Iron-Induced Post-traumatic Epilepsy.

Post-traumatic epilepsy (PTE) is the consequence of traumatic brain damage (TBI), which poses an important health risk for the human population. The underlying mechanism of PTE is complex and appears to be linked with various cellular processes, including oxidative stress and neuroinflammation. Over the years, it has been recognized that most of the available antiseizure medicines are ineffective in preventing PTE. As a result, there is an urgent need to search for alternate treatment options. Naringenin is a flavonoid with multiple pharmacological properties and has shown beneficial effects in several health issues, including neurological disorders. In this study, we investigated the effect of naringenin-loaded polycaprolactone nanoparticles (NarNPs) on neuroinflammatory response in the PTE model. NarNPs were produced using the nanoprecipitation method, and their physicochemical properties were examined by DLS, TEM and AFM. To induce epilepsy in rats, FeCl3 was injected intracortically, and naringenin (NAR), both free NAR and NarNPs, were administered orally, 15 days post-surgery. Epileptic seizures were observed by electroencephalography (EEG) patterns and spectral power analysis of γ-waves. Immunofluorescence analysis of GFAP, IBA1 and TNF-α was performed to examine the disease-modifying potential of NarNPs. Our findings demonstrated that NarNPs marginally reduced epileptiform seizure activity in epileptic rats. Further, the study reported that NarNPs lowered the expression of GFAP, IBA1, and TNF-α. Overall, our data imply that NarNPs have antiseizure and disease-modifying potential by attenuating glial activation and TNF-α production in PTE rats.