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Sustained blood glutamate scavenging enhances protection in ischemic stroke
Communications Biology ( IF 5.2 ) Pub Date : 2020-12-03 , DOI: 10.1038/s42003-020-01406-1
Ahlem Zaghmi 1 , Antonio Dopico-López 2 , María Pérez-Mato 2, 3 , Ramón Iglesias-Rey 2 , Pablo Hervella 2 , Andrea A Greschner 1 , Ana Bugallo-Casal 2 , Andrés da Silva 2 , María Gutiérrez-Fernández 3 , José Castillo 2 , Francisco Campos Pérez 2 , Marc A Gauthier 1
Affiliation  

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.



中文翻译:


持续的血液谷氨酸清除增强对缺血性中风的保护



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着且长期升高导致神经元细胞死亡。本研究探讨了生物共轭形式的谷氨酸草酰乙酸转氨酶 (hrGOT) 的保护作用,该酶在单次给药后约 6 天内催化血液中谷氨酸的消耗。与用盐水治疗的大鼠相比,用这种生物结合物治疗时,缺血大鼠的梗塞体积显着减少,感觉运动功能得到更好的保留。此外,在一些测试中,同等剂量的天然 hrGOT 产生了与盐水治疗组相似的结果。将生物结合物靶向血脑屏障并没有改善其性能。数据表明,生物结合物通过破坏体内不同谷氨酸库之间的稳态,将谷氨酸从大脑中吸出。

更新日期:2020-12-03
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