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: Ruth Prieto, Barbara Tavazzi, Keisuke Taya, Laura Barrios, Angela M Amorini, Valentina Di Pietro, José M Pascual, Anthony Marmarou, Christina R Marmarou
• Journal: Brain research (Brain Res) Vol. 1404 Pg. 39-49 (Aug 02 2011) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 21723535 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Neuroprotective Agents
• NAD
• Aspartic Acid
• Adenosine Triphosphate
• N-acetylaspartate
• Glutathione
• Ascorbic Acid
• Sodium Lactate

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Ascorbic Acid (metabolism)
• Aspartic Acid (analogs & derivatives, metabolism)
• Blood Gas Analysis
• Blood Pressure (drug effects, physiology)
• Brain Chemistry (drug effects, physiology)
• Brain Injuries (etiology, pathology, prevention & control)
• Cerebral Cortex (metabolism)
• Chromatography, High Pressure Liquid (methods)
• Disease Models, Animal
• Energy Metabolism (drug effects, physiology)
• Glutathione (metabolism)
• Male
• Models, Biological
• NAD (metabolism)
• Neuroprotective Agents (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Sodium Lactate (therapeutic use)