In previous studies, we have shown that by increasing the brain-to-blood
glutamate efflux upon scavenging blood
glutamate with either
oxaloacetate or
pyruvate, one achieves highly significant neuroprotection particularly in the context of
traumatic brain injury. The current study examines, for the first time, how the blood
glutamate scavenging properties of
glutamate-
pyruvate transaminase (GPT), alone or in combination with
pyruvate, may contribute to the spectrum of its neuroprotective mechanisms and improve the outcome of rats exposed to
brain ischemia, as they do after
head trauma. Rats that were exposed to permanent
middle cerebral artery occlusion (MCAO) and treated with intravenous 250 mg/kg
pyruvate had a smaller volume of
infarction and reduced
brain edema, resulting in an improved neurological outcome and reduced mortality compared to control rats treated with saline. Intravenous
pyruvate at the low dose of 31.3 mg/kg did not demonstrate any neuroprotection. However, when combined with 0.6 mg/kg of GPT there was a similar neuroprotection observed as seen with
pyruvate at 250 mg/kg. Animals treated with 1.69 g/kg
glutamate had a worse neurological outcome and a larger extent of
brain edema. The decrease in mortality, infarcted brain volume and
edema, as well as the improved neurological outcome following MCAO, was correlated with a decrease in blood
glutamate levels. We therefore suggest that the blood
glutamate scavenging activity of GPT and
pyruvate contributes to the spectrum of their neuroprotective mechanisms and may serve as a new neuroprotective strategy for the treatment of
ischemic stroke.