Scavenging of blood glutamate for enhancing brain-to-blood glutamate efflux

Li,Yunhong; Hou,Xiaolin; Qi,Qi; Wang,Le; Luo,Lan; Yang,Shaoqi; Zhang,Yumei; Miao,Zhenhua; Zhang,Yanli; Wang,Fei; Wang,Hongyan; Huang,Weidong; Wang,Zhenhai; Shen,Ying; Wang,Yin

doi:10.3892/mmr.2013.1793

Scavenging of blood glutamate for enhancing brain-to-blood glutamate efflux

Authors:
- Yunhong Li
- Xiaolin Hou
- Qi Qi
- Le Wang
- Lan Luo
- Shaoqi Yang
- Yumei Zhang
- Zhenhua Miao
- Yanli Zhang
- Fei Wang
- Hongyan Wang
- Weidong Huang
- Zhenhai Wang
- Ying Shen
- Yin Wang
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Affiliations: Department of Neurobiology of Basic Medical College, Center of Scientific Technology, Key Laboratory of Cranial Cerebral Diseases, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Department of Cell Biology and Medical Genetics, Kunming Medical University, Kunming, Yunnan 650500, P.R. China, Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China
Published online on: November 12, 2013 https://doi.org/10.3892/mmr.2013.1793
Pages: 305-310

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Abstract

The presence of excess glutamate in the brain interstitial fluid characterizes several acute pathological conditions of the brain, including traumatic brain injury and stroke. It has been demonstrated that it is possible to eliminate excess glutamate in the brain by decreasing blood glutamate levels and, accordingly, accelerating the brain-to-blood glutamate efflux. It is feasible to accomplish this process by activating blood resident enzymes in the presence of the respective glutamate cosubstrates. In the present study, several glutamate cosubstrates and cofactors were studied in an attempt to identify the optimal conditions to reduce blood glutamate levels. The administration of a mixture of 1 mM pyruvate and oxaloacetate (Pyr/Oxa) for 1 h decreased blood glutamate levels by ≤50%. The addition of lipoamide to this mixture resulted in a further reduction in blood glutamate levels of >80%. In addition, in vivo experiments showed that lipoamide together with Pyr/Oxa is able to decrease blood glutamate levels to a greater extent than Pyr/Oxa alone, and accordingly, this enhances the glutamate efflux from the brain to the blood. These results may outline a novel neuroprotective strategy with increased effectiveness for the removal of excess brain glutamate in various neurodegenerative conditions.

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