As
ischemic stroke is associated with an excessive release of
glutamate into the neuronal extracellular space, a decrease in blood
glutamate levels could provide a mechanism to remove it from the brain tissue, by increasing the brain-blood gradient. In this regard, the ability of
glutamate oxaloacetate transaminase (GOT) to metabolize
glutamate in blood could represent a potential neuroprotective tool for
ischemic stroke. This study aimed to determine the
neuroprotective effects of GOT in an animal model of
cerebral ischemia by means of a middle cerebral
arterial occlusion (MCAO) following the
Stroke Therapy Academic Industry Roundtable (STAIR) group guidelines. In this animal model,
oxaloacetate-mediated GOT activation inhibited the increase of blood and cerebral
glutamate after MCAO. This effect is reflected in a reduction of
infarct size, smaller
edema volume, and lower sensorimotor deficits with respect to controls. Magnetic resonance spectroscopy confirmed that the increase of
glutamate levels in the brain parenchyma after MCAO is inhibited after
oxaloacetate-mediated GOT activation. These findings show the capacity of the GOT to remove
glutamate from the brain by means of blood
glutamate degradation, and suggest the applicability of this
enzyme as an efficient and novel neuroprotective tool against
ischemic stroke.