Zaghmi Ahlem, Dopico-López Antonio, Pérez-Mato María, Iglesias-Rey Ramón, Hervella Pablo, Greschner Andrea A, Bugallo-Casal Ana, da Silva Andrés, Gutiérrez-Fernández María, Castillo José, Pérez Francisco Campos, Gauthier Marc A
Institut National de la Recherche Scientifique (INRS), EMT Research Center, Varennes, Qc, J3X 1S2, Canada.
Clinical Neuroscience Research Laboratory, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
Commun Biol. 2020 Dec 3;3(1):729. doi: 10.1038/s42003-020-01406-1.
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 ~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.
中风是发病、死亡和残疾的主要原因。在缺血性中风期间，大脑中谷氨酸浓度显著且持续升高会导致神经元细胞死亡。本研究探讨了谷氨酸草酰乙酸转氨酶（hrGOT）的生物共轭形式的保护作用，单次给药后，该酶可催化血液中谷氨酸的消耗，持续约6天。与用生理盐水治疗的缺血大鼠相比，用这种生物共轭物治疗的大鼠梗死体积显著减小，感觉运动功能保留得更好。此外，在一些测试中，等量的天然hrGOT产生的结果与生理盐水治疗组相似。将生物共轭物靶向血脑屏障并不能改善其性能。数据表明，生物共轭物通过改变体内不同谷氨酸池之间的稳态，将谷氨酸从大脑中吸出。
