Protective Effects of Intranasally Administrated Oxytocin-Loaded Nanoparticles on Pentylenetetrazole-Kindling Epilepsy in Terms of Seizure Severity, Memory, Neurogenesis, and Neuronal Damage

Abstract

Pentylenetetrazole (PTZ)-induced kindling is an animal model for studying human temporal lobe epilepsy (TLE), which is characterized by alterations of hippocampal neurons and memory. Although the intranasal (IN) administration of oxytocin (OT) has limited efficiency, nanoparticles (NPs) are a promising candidate to deliver OT to the brain. However, there are very limited data on epilepsy research about oxytocin-loaded nanoparticles (NP-OTs). The aim of this study is to investigate the effects of IN administration of chronic NP-OTs on the hippocampus of PTZ-induced male epileptic rats in terms of seizure severity, memory, neurogenesis, and neuronal damage. Saline/OT/NP-OTs were administrated to both control (Ctrl) and PTZ groups intranasally. Consequently, saline and PTZ were injected, respectively, 25 times every 48 h. Then, seizure severity (score and latency) was calculated for the PTZ groups. A spatial working memory evaluation test (SWMET) was performed after the last injection. Hippocampus histopathology, neurogenesis, and apoptosis were demonstrated. Serum total antioxidant status (TAS) and total oxidant status (TOS) levels and the oxidative stress index (OSI) were measured. We showed that OTs and NP-OTs prevented the kindling development and had positive effects on seizure severity. SWMET-related behaviors were also recovered in the PTZ + NP-OT group. A significant increase of neurogenesis and decrease of apoptosis in the hippocampus of the PTZ + NP-OT group were observed, while OTs and NP-OTs had protective effects against PTZ-induced damage to hippocampal neurons. Our results indicate that the chronic administration of NP-OTs may have positive effects on hippocampal damage via increasing neurogenesis and decreasing apoptosis and seizure severity.