Neuroprotection by glutamate oxaloacetate transaminase in ischemic stroke: an experimental study.
As ischemic stroke is associated with an excessive release of glutamate into the neuronal extracellular space, a decrease in blood glutamate levels could provide a mechanism to remove it from the brain tissue, by increasing the brain-blood gradient. In this regard, the ability of glutamate oxaloacetate transaminase (GOT) to metabolize glutamate in blood could represent a potential neuroprotective tool for ischemic stroke. This study aimed to determine the neuroprotective effects of GOT in an animal model of cerebral ischemia by means of a middle cerebral arterial occlusion (MCAO) following the Stroke Therapy Academic Industry Roundtable (STAIR) group guidelines. In this animal model, oxaloacetate-mediated GOT activation inhibited the increase of blood and cerebral glutamate after MCAO. This effect is reflected in a reduction of infarct size, smaller edema volume, and lower sensorimotor deficits with respect to controls. Magnetic resonance spectroscopy confirmed that the increase of glutamate levels in the brain parenchyma after MCAO is inhibited after oxaloacetate-mediated GOT activation. These findings show the capacity of the GOT to remove glutamate from the brain by means of blood glutamate degradation, and suggest the applicability of this enzyme as an efficient and novel neuroprotective tool against ischemic stroke.
Department of Neurology, Clinical Neuroscience Research Laboratory, Hospital Clínico Universitario, University of Santiago de Compostela, IDIS, Santiago de Compostela, Spain. francampos@linc-stg.eu
Francisco
F
Campos
Tomás
T
Sobrino
Pedro
P
Ramos-Cabrer
Bárbara
B
Argibay
Jesús
J
Agulla
María
M
Pérez-Mato
Raquel
R
Rodríguez-González
David
D
Brea
José
J
Castillo
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D018698:Glutamic Acid / Q000097:blood*; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D062907:Oxaloacetic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D062907:Oxaloacetic Acid; D018698:Glutamic Acid; D001219:Aspartate Aminotransferases
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