title: Brain energy depletion in a rodent model of diffuse traumatic brain injury is not prevented with administration of sodium lactate.
abstract: Lactate has been identified as an alternative fuel for the brain in situations of increased energy demand, as following a traumatic brain injury (TBI). This study investigates the effect of treatment with sodium lactate (NaLac) on the changes in brain energy state induced by a severe diffuse TBI. Rats were assigned to one of the eight groups (n=10 per group): 1-sham, normal saline; 2-TBI, normal saline; 3-TBI, hypertonic saline; 4-TBI, 100mM NaLac, 5-TBI, 500 mM NaLac; 6-TBI, 1280 mM NaLac; 7-TBI, 2000 mM NaLac and 8-TBI-500 mM NaLac+magnesium sulfate. Cerebrums were removed 6h after trauma. Metabolites representative of the energy state (ATP, ATP-catabolites), N-acetylaspartate (NAA), antioxidant defenses (ascorbic acid, glutathione), markers of oxidative stress (malondialdehyde, ADP-ribose) and nicotinic coenzymes (NAD(+)) were measured by HPLC. TBI induced a marked decrease in the cerebral levels of ATP, NAA, ascorbic acid, glutathione and NAD(+) and a significant rise in the content of ATP-catabolites, malondialdehyde and ADP-ribose. These alterations were not ameliorated with NaLac infusion. We observed a significant reduction in cerebral NAD(+), an essential co-enzyme for mitochondrial lactate-dehydrogenase that converts lactate into pyruvate and thus replenishes the tricarboxylic acid cycle. These results suggest that the metabolic pathway necessary to consume lactate may be compromised following a severe diffuse TBI in rats.
authors: Department of Neurosurgery, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA 23298-0508, USA. rprieto29@hotmail.com
authors: Ruth
authors: R
authors: Prieto
authors: Barbara
authors: B
authors: Tavazzi
authors: Keisuke
authors: K
authors: Taya
authors: Laura
authors: L
authors: Barrios
authors: Angela M
authors: AM
authors: Amorini
authors: Valentina
authors: V
authors: Di Pietro
authors: José M
authors: JM
authors: Pascual
authors: Anthony
authors: A
authors: Marmarou
authors: Christina R
authors: CR
authors: Marmarou
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009243:NAD / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019354:Sodium Lactate / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D009243:NAD; D001224:Aspartic Acid; D000255:Adenosine Triphosphate; C000179:N-acetylaspartate; D005978:Glutathione; D001205:Ascorbic Acid; D019354:Sodium Lactate