Targeted Delivery of Quercetin-Loaded Magnetic Nanoparticles Decrease Seizure Activity and Ameliorate Kainate-Induced Memory Disturbances in the Animal Models of Epilepsy
Journal Title: The 2nd Annual Meeting of International Center for Neuroscience Research - Year 2021, Vol 2, Issue 1
Abstract
Epilepsy is chronic neurological disease affecting roughly 1% of the human population. It is characterized by periodic repetitive seizures and associated cognitive impairments. Almost 30% of epileptic cases are refractory to the current drugs. Temporal lobe epilepsy (TLE) is one of the most resistant type of epilepsy. Studies have indicated that the loss of inhibitory neurons in the hippocampus during status epilepticus (SE) induces hyperexcitability that initiates reactive gliosis. These lead to mitochondrial dysfunction in neurons due to the generation of free radicals of oxygen and nitrogen species within the hippocampus and dentate gyrus. Free radical induced changes in turn can provoke seizure genesis and related cell death, thus could play important role in the pathogenesis of epilepsy. In recent years the new treatment strategies of epileptic disorder focuse on flavonoids - plant derived antioxidants. Quercetin is one of the best candidates for this purpose. Despite of the variety of many promising antioxidant and antiepileptic properties of Quercetin, poor bioavailability strongly limits its biological effects in vivo. The modern approach to solve mentioned problem is usage of nanoparticles (NP). It is shown that nanoparticles protect, control the release and increase the influence of bioactive compounds to the target area. The aim of our research was to load the magnetic nanoparticles (MNP) with the Quercetin (Q-MNP) and in the presence of unilateral exposure of the external static magnetic field (ESMF) on the temporal lobe projection investigate the influence of Q-MNP on behavioral, morphological and electrophysiological alterations induced by the kainic acid model of TLE. Systemic administration of Q-MNP with the presence of ESMF but not quercetin alone showed statistically significant reduction of the seizure appearance and improvement of epilepsy-induced memory impairment. Q-MNPs without ESMF was ineffective. Following morphological experiments revealed that the number of iron inserts are significantly higher in the ESMF-exposure site compare with the untreated contralateral site, suggesting that the exposure of magnetic field improves target-delivery of the Q-MNP to the brain. Injection of Q-MNP with the presence of ESMF significantly decrease the amplitude and frequency of neuronal discharges in the hippocampus. The effect of Q-MNP in the CA1 field of the hippocampus was inhibitory, which could explain how it ameliorates behavioral and morphological disturbances caused by SE. Supported by Rustaveli Foundation, grant FR17_629.
Authors and Affiliations
N. Doreulee*, M. Qurasbediani, G. Kutelia, M. Chikovani, B. Chkhartisvili, R. Bukia, B. Partsvania
Keywords
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