Dergi makalesi Açık Erişim

Sustained blood glutamate scavenging enhances protection in ischemic stroke

2020    Zaghmi, Ahlem; Dopico-Lopez, Antonio; Perez-Mato, Maria; Iglesias-Rey, Ramon; Hervella, Pablo; Greschner, Andrea A.; Bugallo-Casal, Ana; da Silva, Andres; Gutierrez-Fernandez, Maria; Castillo, Jose; Perez, Francisco Campos; Gauthier, Marc A.

Stroke is a major cause of morbidity, mortality, and disability. During ischemic stroke, a marked and prolonged rise of glutamate concentration in the brain causes neuronal cell death. This study explores the protective effect of a bioconjugate form of glutamate oxaloacetate transaminase (hrGOT), which catalyzes the depletion of blood glutamate in the bloodstream for similar to 6 days following a single administration. When treated with this bioconjugate, a significant reduction of the infarct volume and a better retention of sensorimotor function was observed for ischemic rats compared to those treated with saline. Moreover, the equivalent dose of native hrGOT yielded similar results to the saline treated group for some tests. Targeting the bioconjugate to the blood-brain-barrier did not improve its performance. The data suggest that the bioconjugates draw glutamate out of the brain by displacing homeostasis between the different glutamate pools of the body.