Blood glutamate grabbing does not reduce the hematoma in an intracerebral hemorrhage model but it is a safe excitotoxic treatment modality.
Recent studies have shown that blood glutamate grabbing is an effective strategy to reduce the excitotoxic effect of extracellular glutamate released during ischemic brain injury. The purpose of the study was to investigate the effect of two of the most efficient blood glutamate grabbers (oxaloacetate and recombinant glutamate oxaloacetate transaminase 1: rGOT1) in a rat model of intracerebral hemorrhage (ICH). Intracerebral hemorrhage was produced by injecting collagenase into the basal ganglia. Three treatment groups were developed: a control group treated with saline, a group treated with oxaloacetate, and a final group treated with human rGOT1. Treatments were given 1 hour after hemorrhage. Hematoma volume (analyzed by magnetic resonance imaging (MRI)), neurologic deficit, and blood glutamate and GOT levels were quantified over a period of 14 days after surgery. The results observed showed that the treatments used induced a significant reduction of blood glutamate levels; however, they did not reduce the hematoma, nor did they improve the neurologic deficit. In the present experimental study, we have shown that this novel therapeutic strategy is not effective in case of ICH pathology. More importantly, these findings suggest that blood glutamate grabbers are a safe treatment modality that can be given in cases of suspected ischemic stroke without previous neuroimaging.
Clinical Neurosciences Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
Andrés
A
da Silva-Candal
Clinical Neurosciences Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
Alba
A
Vieites-Prado
Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autónoma University of Madrid, Madrid, Spain.
María
M
Gutiérrez-Fernández
Clinical Neurosciences Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
Ramón I
RI
Rey
Clinical Neurosciences Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
Bárbara
B
Argibay
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
David
D
Mirelman
Clinical Neurosciences Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
Tomás
T
Sobrino
Neuroscience and Cerebrovascular Research Laboratory, Department of Neurology and Stroke Center, La Paz University Hospital, Neuroscience Area of IdiPAZ Health Research Institute, Autónoma University of Madrid, Madrid, Spain.
Berta
B
Rodríguez-Frutos
Clinical Neurosciences Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
José
J
Castillo
Clinical Neurosciences Research Laboratory, Department of Neurology, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.
Francisco
F
Campos
D000818:Animals; D024443:Aspartate Aminotransferase, Cytoplasmic / Q000627:therapeutic use*; D002543:Cerebral Hemorrhage / Q000097:blood* / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D057487:Enzyme Therapy; D018698:Glutamic Acid / Q000097:blood*; D006406:Hematoma / Q000097:blood* / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D062907:Oxaloacetic Acid / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use
D011994:Recombinant Proteins; D062907:Oxaloacetic Acid; D018698:Glutamic Acid; D024443:Aspartate Aminotransferase, Cytoplasmic