Rapamycin provides anti-epileptogenic effect in a rat model of post-traumatic epilepsy via deactivation of mTOR signaling pathway

Abstract

The mammalian target of rapamycin (mTOR) signaling pathway has attracted much attention in recent years. However, the contribution of mTOR activation to the development of post-traumatic epilepsy (PTE) remains largely unknown. The purpose of the present study was to investigate the activation of mTOR signaling in a rat model of FeCl2 -induced PTE, and to explore the potential effect of its specific inhibitor rapamycin. The results indicated that the expression levels of p-mTOR and p-P70S6K, the overactivation biomarkers of mTOR signaling, increased significantly in hippocampal and perilesional cortex following PTE induction. Notably, they were significantly decreased in the aformementioned brain regions following rapamycin treatment. Furthermore, the frequency and number of behavioral seizures and epileptic brain injury were also greatly reduced. These results suggest that hyperactivation of the mTOR signaling pathway is a crucial mechanism of PTE development, and it may be considered a novel therapeutic target for PTE treatment.