Rapamycin treatment improves neuron viability in an in vitro model of stroke.

Abstract

Ischemic stroke is the leading cause of serious, long-term adult disability and is associated with sensorimotor and cognitive impairments due to neuronal degeneration. Currently, recombinant tissue plasminogen activator (rTPA) is the only FDA-approved medical therapy for treatment of patients with acute ischemic stroke. However, rTPA can only be given within 3 hours of symptom onset, and only 2% of patients are eligible. Therefore, there is an urgent need for novel neuroprotective treatment options for ischemic stroke. An emerging treatment for a diverse range of neurological disorders associated with neurodegeneration is rapamycin, a key modulator of the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway is the primary regulator of the cellular response to nutrient availability, changes in energy status and stress as seen following ischemia and reperfusion. However, rapamycin's effects on mTORC1 and mTORC2 are poorly understood in neurons. In the current study we show that rapamycin can prevent the activation of both mTORC1 and mTORC2 in cortical neurons and improve cell survival following oxygen glucose deprivation (OGD), an in vitro model of ischemic stroke. This work further supports the investigation of rapamycin as a novel neuroprotectant for ischemic stroke.