期刊
NEUROBIOLOGY OF DISEASE
卷 106, 期 -, 页码 244-254出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2017.07.012
关键词
Energy metabolism; Glucose utilization; Tetanus toxin; Kindling; Alzheimer's disease epilepsy; Seizures; Neuronal excitability
资金
- French National Research Agency METANEX grant [ANR-2010-BLAN-1443-01]
- Alzheimer's Association [NESAD-12-242486]
- Russian Foundation for Fundamental Investigations [15-34-20871, 15-04-99683]
- KID
- Russian Science Foundation [17-75-20245] Funding Source: Russian Science Foundation
Metabolic intervention strategy of epilepsy treatment has been gaining broader attention due to accumulated evidence that hypometabolism, manifested in humans as reduced brain glucose consumption, is a principal factor in acquired epilepsy. Therefore, targeting deficient energy metabolism may be an effective approach for treating epilepsy. To confront this pathology we utilized pyruvate, which besides being an anaplerotic mitochondrial fuel possesses a unique set of neuroprotective properties as it: (i) is a potent reactive oxygen species scavenger; (ii) abates overactivation of Poly [ADP-ribose] polymerase 1 (PARP-1); (iii) facilitates glutamate efflux from the brain; (iv) augments brain glycogen stores; (v) is anti-inflammatory; (vi) prevents neuronal hyperexcitability; and (vii) normalizes the cytosolic redox state. In vivo, chronic oral pyruvate administration completely abolished established epileptic phenotypes in three accepted and fundamentally different rodent acquired epilepsy models. Our study reports metabolic correction by pyruvate as a potentially highly effective treatment of acquired epilepsies. (C) 2017 Elsevier Inc. All rights reserved.
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