Beyond Glutamate Antagonists for Treatment of Ischemic Stroke: Blood Glutamate Grabbing

Glutamate-excitotoxicity is a primary contributor of ischemic neuronal death. Several strategies have been developed against glutamate-excitotoxicity, however any of them have not showed positive results in the clinical practice so far. Nowadays, the concept of blood/brain glutamate grabbing is well recognized as a novel and attractive protective strategy to reduce the excitotoxic effect of excess extracellular glutamate that accumulates in the brain following an ischemic stroke. The main advantage of this novel therapeutic strategy is that occurs in the blood circulation and therefore does not affect the normal brain neurophysiology, as it has been described for other drug treatments used against glutamate excitotoxicity. In this work, we summarize all experimental data about the potential application of this therapy against stroke pathology. Ischemic stroke, caused by interruption of the blood supply to the brain, is one of the most important causes of morbidity and mortality worldwide. Currently, the control of systemic parameters, such as body temperature, blood pressure, and glycemia, has considerably improved the outcome of stroke patients. In the absence of protective therapy, an early artery reperfusion, i.e. mechanical or enzymatic thrombolysis, remains the primary goal of treatment for acute ischemic stroke. However, because of the progressive increase in stroke incidence, the high morbidity and the limited therapeutic tools against stroke, seeking new alternatives that can be applied more universally and with less technological requirements is in high demand1, 2.