TY - JOUR
T1 - The contribution of the blood glutamate scavenging activity of pyruvate to its neuroprotective properties in a rat model of closed head injury
AU - Zlotnik, Alexander
AU - Gurevich, Boris
AU - Cherniavsky, Evgenia
AU - Tkachov, Sergei
AU - Matuzani-Ruban, Angela
AU - Leon, Avner
AU - Shapira, Yoram
AU - Teichberg, Vivian I.
N1 - Funding Information:
Acknowledgments 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.
PY - 2008/6
Y1 - 2008/6
N2 - 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.
AB - 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.
KW - Antioxidant activity
KW - Blood glutamate levels
KW - Blood glutamate scavenging
KW - Brain to blood glutamate efflux
KW - Closed head injury
KW - Excitotoxicity
KW - Glutamate
KW - Glutamate-pyruvate transaminase
KW - Neurological outcome
KW - Neuroprotection
KW - Oxaloacetate
KW - Pyruvate
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=42149171720&partnerID=8YFLogxK
U2 - 10.1007/s11064-007-9548-x
DO - 10.1007/s11064-007-9548-x
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C2 - 18080187
AN - SCOPUS:42149171720
SN - 0364-3190
VL - 33
SP - 1044
EP - 1050
JO - Neurochemical Research
JF - Neurochemical Research
IS - 6
ER -