Blood
glutamate scavenging is a novel and attractive protecting strategy to reduce the excitotoxic effect of extracellular
glutamate released during ischemic
brain injury.
Glutamate oxaloacetate transaminase 1 (GOT1) activation by means of
oxaloacetate administration has been used to reduce the
glutamate concentration in the blood. However, the protective effect of the administration of the recombinant GOT1 (rGOT1)
enzyme has not been yet addressed in
cerebral ischemia. The aim of this study was to analyze the protective effect of an effective dose of
oxaloacetate and the human rGOT1 alone and in combination with a non-effective dose of
oxaloacetate in an animal model of
ischemic stroke. Sixty rats were subjected to a transient
middle cerebral artery occlusion (MCAO).
Infarct volumes were assessed by magnetic resonance imaging (MRI) before treatment administration, and 24 h and 7 days after MCAO. Brain
glutamate levels were determined by in vivo MR spectroscopy (MRS) during artery occlusion (80 min) and reperfusion (180 min). GOT activity and serum
glutamate concentration were analyzed during the occlusion and reperfusion period. Somatosensory test was performed at baseline and 7 days after MCAO. The three treatments tested induced a reduction in serum and brain
glutamate levels, resulting in a reduction in
infarct volume and sensorimotor deficit. Protective effect of rGOT1 supplemented with
oxaloacetate at 7 days persists even when treatment was delayed until at least 2 h after onset of
ischemia. In conclusion, our findings indicate that the combination of human rGOT1 with low doses of
oxaloacetate seems to be a successful approach for
stroke treatment.