Beneficial Effects of Kaempferol after Developmental Traumatic Brain Injury Is through Protection of Mitochondrial Function, Oxidative Metabolism, and Neural Viability
Oxidative energy metabolism is depressed after mild/moderate traumatic brain injury (TBI) during early development, accompanied by behavioral debilitation and secondary neuronal death. A TBI metabolome analysis revealed broad effects with a striking impact on energy metabolism. Our studies on mitoch...
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Published in | Journal of neurotrauma Vol. 36; no. 8; pp. 1264 - 1278 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
Mary Ann Liebert, Inc
15.04.2019
Mary Ann Liebert, Inc., publishers |
Subjects | |
Online Access | Get full text |
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Summary: | Oxidative energy metabolism is depressed after mild/moderate traumatic brain injury (TBI) during early development, accompanied by behavioral debilitation and secondary neuronal death. A TBI metabolome analysis revealed broad effects with a striking impact on energy metabolism. Our studies on mitochondrial modulators and their effects on brain function have shown that kaempferol, a stimulator of the mitochondrial Ca
uniporter channel (mCU), enhanced neural and neurovascular activity in the normal brain and improved stimulus-induced brain activation and behavior after TBI during early development. Because kaempferol enhances mitochondrial Ca
uptake and cycling, with protective effects after TBI, we tested the hypothesis that kaempferol treatment during the acute/subacute stage after TBI (0-72 h) acted on mitochondria in improving TBI outcome. Developmental age rats (P31) underwent TBI and were treated with vehicle or kaempferol (1 mg/kg intraperitoneally) in three doses at 1, 24, and 48 h after TBI. Brains were harvested at 72 h and subjected to liquid chromatography mass spectrometric measurements. Decrease in pyruvate and tricarboxylic acid (TCA) cycle flux were observed in the untreated and vehicle-treated group, consistent with previously established energy metabolic decline after TBI. Kaempferol improved TCA cycle flux, maintained mitochondrial functional integrity as observed by decreased acyl carnitines, improved neural viability as evidenced by higher N-acetyl aspartate levels. The positive outcomes of kaempferol on metabolic profile corresponded with improved sensorimotor behavior. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0897-7151 1557-9042 |
DOI: | 10.1089/neu.2018.6100 |