Metabolic acetate therapy for the treatment of traumatic brain injury.
Patients suffering from traumatic brain injury (TBI) have decreased markers of energy metabolism, including N-acetylaspartate (NAA) and ATP. In the nervous system, NAA-derived acetate provides acetyl-CoA required for myelin lipid synthesis. Acetate can also be oxidized in mitochondria for the derivation of metabolic energy. In the current study, using the controlled cortical impact model of TBI in rats, we investigated the effects of the hydrophobic acetate precursor, glyceryltriacetate (GTA), as a method of delivering metabolizable acetate to the injured brain. We found that GTA administration significantly increased the levels of both NAA and ATP in the injured hemisphere 4 and 6 days after injury, and also resulted in significantly improved motor performance in rats 3 days after injury.
Arun
Peethambaran
P
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Ariyannur
Prasanth S
PS
Moffett
John R
JR
Xing
Guoqiang
G
Hamilton
Kristen
K
Grunberg
Neil E
NE
Ives
John A
JA
Namboodiri
Aryan M A
AM
D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D019342:Acetic Acid / Q000378:metabolism*; D000105:Acetyl Coenzyme A / Q000096:biosynthesis*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008297:Male; D008563:Membrane Lipids / Q000096:biosynthesis; D009186:Myelin Sheath / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014215:Triacetin / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000085:Acetates; D008563:Membrane Lipids; D018696:Neuroprotective Agents; D001224:Aspartic Acid; D000105:Acetyl Coenzyme A; C000179:N-acetylaspartate; D019342:Acetic Acid; D014215:Triacetin