title: Human recombinant glutamate oxaloacetate transaminase 1 (GOT1) supplemented with oxaloacetate induces a protective effect after cerebral ischemia.
abstract: Blood glutamate scavenging is a novel and attractive protecting strategy to reduce the excitotoxic effect of extracellular glutamate released during ischemic brain injury. Glutamate oxaloacetate transaminase 1 (GOT1) activation by means of oxaloacetate administration has been used to reduce the glutamate concentration in the blood. However, the protective effect of the administration of the recombinant GOT1 (rGOT1) enzyme has not been yet addressed in cerebral ischemia. The aim of this study was to analyze the protective effect of an effective dose of oxaloacetate and the human rGOT1 alone and in combination with a non-effective dose of oxaloacetate in an animal model of ischemic stroke. Sixty rats were subjected to a transient middle cerebral artery occlusion (MCAO). Infarct volumes were assessed by magnetic resonance imaging (MRI) before treatment administration, and 24 h and 7 days after MCAO. Brain glutamate levels were determined by in vivo MR spectroscopy (MRS) during artery occlusion (80 min) and reperfusion (180 min). GOT activity and serum glutamate concentration were analyzed during the occlusion and reperfusion period. Somatosensory test was performed at baseline and 7 days after MCAO. The three treatments tested induced a reduction in serum and brain glutamate levels, resulting in a reduction in infarct volume and sensorimotor deficit. Protective effect of rGOT1 supplemented with oxaloacetate at 7 days persists even when treatment was delayed until at least 2 h after onset of ischemia. In conclusion, our findings indicate that the combination of human rGOT1 with low doses of oxaloacetate seems to be a successful approach for stroke treatment.
authors.affiliation: Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pérez-Mato
authors.affiliation: Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Ramos-Cabrer
authors.affiliation: Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Sobrino
authors.affiliation: Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Blanco
authors.affiliation: Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Ruban
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Mirelman
authors.affiliation: 1] Josep Carreras Leukemia Research Institute, Cell Therapy Program of the University of Barcelona, Barcelona, Spain [2] Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Menendez
authors.affiliation: Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Castillo
authors.affiliation: Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Campos
mesh_terms: D000818:Animals; D024443:Aspartate Aminotransferase, Cytoplasmic / Q000008:administration & dosage* / Q000097:blood / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000201:enzymology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D062907:Oxaloacetic Acid / Q000008:administration & dosage* / Q000097:blood; D020011:Protective Agents / Q000008:administration & dosage* / Q000378:metabolism; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020011:Protective Agents; D062907:Oxaloacetic Acid; D024443:Aspartate Aminotransferase, Cytoplasmic