Mechanistic target of rapamycin (mTOR) signaling in status epilepticus

The mechanistic target of rapamycin (mTOR) pathway plays a critical role in brain development, neuronal shape and size, and synaptic plasticity, as well as learning and memory. Mutations in mTOR pathway genes (MPG) cause malformations of cortical development (MCDs) that are highly associated with often intractable epilepsy, thus highlighting an association between the mTOR pathway and establishment of the epileptic network. A growing body of preclinical evidence in in vitro and rodent model systems suggests that mTOR signaling may be altered in status epilepticus (SE) and that modulation of mTOR activation with mTOR inhibitors such as rapamycin (sirolimus) could provide new therapeutic avenues for treatment of both refractory epilepsy and SE. Rapamycin may have ubiquitous effects on all neuronal subtypes as well as astrocytes and seems to prevent the development of seizures following experimentally induced SE. To date, there have been no human studies focused on mTOR signaling in SE, but clearly, preclinical data support investigation into this pivotal cell signaling pathway. Thus, modulation of the mTOR pathway may provide a new strategy for treatment of SE and could have implications for the prevention of epilepsy in patients with SE. This article is part of the Special Issue Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures (c) 2019 Published by Elsevier Inc.