The Contribution of the Blood Glutamate Scavenging Activity of Pyruvate to its Neuroprotective Properties in a Rat Model of Closed Head Injury
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The removal of excess glutamate from brain fluids after acute insults such as closed head injury (CHI) and stroke is expected to prevent excitotoxicity and the ensuing long lasting neurological deficits. Since blood glutamate scavenging accelerates the removal of excess glutamate from brain into blood and causes neuroprotection, we have evaluated here whether the neuroprotective properties of pyruvate could be partly accounted to its blood glutamate scavenging activity. The neurological outcome of rats after CHI improved significantly when treated with intravenous pyruvate (0.9 mmoles/100 g) but not with pyruvate administered together with glutamate. Pyruvate, at 5 μmole/100 g rat was neither protective not able to decrease blood glutamate but displayed the latter two properties when combined with 60 μg/100 g of glutamate-pyruvate transaminase. Since the neurological recovery from CHI was correlated with the decrease of blood glutamate levels, we conclude that pyruvate blood glutamate scavenging activity contributes to the spectrum of its neuroprotective mechanisms.
KeywordsGlutamate Excitotoxicity Blood glutamate levels Blood glutamate scavenging Oxaloacetate Pyruvate Glutamate-pyruvate transaminase Closed head injury Stroke Neuroprotection Brain to blood glutamate efflux Neurological outcome Antioxidant activity Intravenous injection
We thank Prof Charles Krieger for his valuable suggestions on our manuscript. This work was supported in part by grants to VIT from the Nella and Leon Benoziyo Center for Neurological Diseases; the Irwin Green Fund for Studying the Development of the Brain, the Carl and Micaela Einhorn-Dominic Institute for Brain Research, and the Weizmann-Negri Fund. The data obtained are part of A.Z’s PhD thesis. VIT is the incumbent of the Louis and Florence Katz-Cohen Chair of Neuropharmacology.
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