Volume 33, Number 6, 1044-1050, DOI: 10.1007/s11064-007-9548-x

The Contribution of the Blood Glutamate Scavenging Activity of Pyruvate to its Neuroprotective Properties in a Rat Model of Closed Head Injury

Alexander Zlotnik, Boris Gurevich, Evgenia Cherniavsky, Sergei Tkachov, Angela Matuzani-Ruban, Avner Leon, Yoram Shapira and Vivian I. Teichberg

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Abstract

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.

Keywords  Glutamate - 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

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