Quercetin-Loade Chitosan-Alginate-STPP Nanoparticles Ameliorate Memory Deficits and Reduce Glial Activation in Pentylenetetrazol- nduced Kindling Model of Epilepsy

Despite several beneficial effects of quercetin, its medical application has been hampered due to low water solubility. To improve the aqueous solubility of quercetin, it has been loaded on chitosan (CS)-alginate (ALG) - sodium tripolyphosphate (STPP) nanoparticles (NPs). Then, the effect of quercetin NPs on memory improvement and glial activation was investigated in pentylenetetrazol (PTZ)-inducedkindling model. Materials and Methods: Male NMRI mice have received the daily injection of quercetin NPs at dose of 25 or 50 mg/kg. All interventions were injected intraperitoneally (i.p), 10 days before PTZ administration and the injections were continueduntil 1 h before each PTZ injection. Animals have received 12 injections of PTZ and then, brain tissues homogenates were provided for assessment of oxidative stress markers, including thiobarbituric acid-reactive substances (TBARS) indicator of lipid peroxidation(LPO) and ferric-reducing ability of plasma (FRAP) indicator of total anti-oxidant capacity. Also, brain tissues were removed for histological evaluation. Nissl staining was used to determine the level of cell death in hippocampus and immunostaining method was performed against NeuN and GFAP/Iba1 for assessment of neuronal density and glial activation respectively.Results: Behavioral results showed that quercetin NPs exhibit anticonvulsant activity and prevent cognitive impairment in fully kindled animals. The level of cell death and glial activation reduced in animals which have received quercetin NPs compared to those received freequercetin. The level of TBARS decreased and FRAP increased in animals which have received quercetin NPs. Conclusion: To conclude, these findings suggest that quercetin NPs effectively ameliorate memory impairment and attenuate the level of activated glial cells in a mice model of chronic epilepsy.