Scavenging of blood glutamate for enhancing brain-to-blood glutamate efflux.
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.
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.
Yunhong
Y
Li
Xiaolin
X
Hou
Qi
Q
Qi
Le
L
Wang
Lan
L
Luo
Shaoqi
S
Yang
Yumei
Y
Zhang
Zhenhua
Z
Miao
Yanli
Y
Zhang
Fei
F
Wang
Hongyan
H
Wang
Weidong
W
Huang
Zhenhai
Z
Wang
Ying
Y
Shen
Yin
Y
Wang
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000737:chemistry* / Q000378:metabolism; D018698:Glutamic Acid / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D062907:Oxaloacetic Acid / Q000737:chemistry / Q000378:metabolism; D019289:Pyruvic Acid / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism
D016166:Free Radical Scavengers; D062907:Oxaloacetic Acid; D018698:Glutamic Acid; D008063:Thioctic Acid; D019289:Pyruvic Acid; C013091:lipoamide