The maintenance of brain extracellular glutamate (Glu) at levels below its excitotoxic threshold is performed by Glu transporters present on glia and neurons as well as on brain capillary endothelial cells which remove brain Glu into blood. The feasibility of accelerating the naturally occurring brainto-blood Glu efflux was studied using paradigms based on the fate of Glu present in the cerebrospinal fluid or infused into the brain ventricles and monitored before, during, and after decreasing blood Glu levels with pyruvate and oxaloacetate, the respective Glu co-substrates of the blood resident enzymes glutamate-pyruvate transaminase and glutamateoxaloacetate transaminase. Results from cerebroventricular perfusions with [ 3 H]Glu, intracerebroventricular injections of [ 3 H]Glu, and measurements of the basal CSF Glu levels point out to the same conclusion that the intravenous administration of pyruvate and oxaloacetate which decreases blood Glu levels accelerates the brain-to-blood Glu efflux. We conclude that the brain extracellular Glu levels can be controlled in part by the blood Glu levels. The results may provide not only a rational explanation for the inhibition of Glu release and neuroprotective effects of parentally administered pyruvate in hemorrhagic shock and forebrain ischemia but could also outline a potential strategy for the removal of excess Glu in various neurodegenerative disorders.

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Extracts of electric organ tissue of Electrophorus electricus contain a saccharide-binding protein, named electrolectin, which agglutinates trypsin-treated rabbit erythrocytes and is specifically inhibited by disaccharides containing nonreducing terminal beta-D-galactosyl residues. Electrolectin seems at least partially membrane-bound but is also found in soluble fractions of homoge-nates from which it can be purfied by affinity chromatography on cross-linked and desulfated agarose (ECD-Sepharose) as a protein of molecular weight 33,000. About 400 mg of electrolectin are present per kg of tissue. It has an affinity for lactose of 1.0 mM-1 and 5.5mM-1 as estimated, respectively, by hapten inhibition and fluorescence spectroscopy. Studies on the distribution of beta-D-galactoside-binding activity in animal tissues reveal particularly high levels in sheletal muscle tissue and in cultures of embryonic skeletal muscle and neuroblastoma cells.

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 micromole/100 g rat was neither protective not able to decrease blood glutamate but displayed the latter two properties when combined with 60 microg/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.