Neuroprotection by glutamate oxaloacetate transaminase in ischemic stroke: an experimental study

• Published in: Journal of cerebral blood flow and metabolism 2011-06, Vol.31 (6), p.1378-1386
• Main Authors: Campos, Francisco, Sobrino, Tomás, Ramos-Cabrer, Pedro, Argibay, Bárbara, Agulla, Jesús, Pérez-Mato, María, Rodríguez-González, Raquel, Brea, David, Castillo, José
• Format: Article
• Language: English
• Subjects: Animals; Aspartate Aminotransferases - metabolism; Biological and medical sciences; Brain - drug effects; Brain - enzymology; Brain - pathology; Brain Ischemia - drug therapy; Brain Ischemia - enzymology; Brain Ischemia - pathology; Cells, Cultured; Endothelial Cells - metabolism; Enzyme Activation - drug effects; Glutamic Acid - blood; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Infarction, Middle Cerebral Artery - enzymology; Infarction, Middle Cerebral Artery - pathology; Magnetic Resonance Imaging; Male; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - therapeutic use; Original; Oxaloacetic Acid - administration & dosage; Oxaloacetic Acid - therapeutic use; Rats; Rats, Sprague-Dawley; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2011.3

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.