Melissa Trotman-Lucas, PhD
Neuroprotective treatments aim to prevent cellular death, particularly neuronal cell death, during ischemic/hypoxic conditions such as in acute ischemic stroke. Maintenance of neuroprotection long-term requires a return of blood and oxygen to the ischemic territory area, not regularly achieved in previous clinical trials. Yet, with recanalization rates of greater than 80%, afforded by the advent of mechanical thrombectomy following ischemic stroke, the return of flow to the ischemic territory is now more consistent. Nevertheless, following the return of blood flow to this area, cellular damage continues to spread and grow due to the phenomenon of “ischemic-reperfusion injury.” This progressive increase in damage indicates a continued need to investigate neuroprotective treatments that could be used alongside recanalization, both thrombolysis and thrombectomy, to recover/prevent long-term cellular damage.
It is well established that calcium (Ca2+) overload plays a key role in neuronal death during ischemic/hypoxic events. In addition to voltage-gated and receptor-mediated Ca2+ influx, there is a further route of entry into the cell, a route switched on in response to depleted intracellular Ca2+ stores. This additional entry route is called capacitative or store operated Ca2+ entry and is thought to contribute to the stabilization of both cytosolic Ca2+ concentration and intracellular Ca2+ stores.