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. 2010 Jan;27(1):293-8.
doi: 10.1089/neu.2009.0994.

Metabolic acetate therapy for the treatment of traumatic brain injury

Peethambaran Arun  1 , Prasanth S Ariyannur, John R Moffett, Guoqiang Xing, Kristen Hamilton, Neil E Grunberg, John A Ives, Aryan M A Namboodiri
Affiliations

Metabolic acetate therapy for the treatment of traumatic brain injury

Peethambaran Arun et al. J Neurotrauma. 2010 Jan.

Abstract

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.

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Figures

FIG. 1.
FIG. 1.
Cresyl violet acetate stained forebrain sections showing CCI injury to the left hemisphere at the level of the septal nucleus (A) and the dorsal hippocampus (B). At the periphery of the injury, the corpus callosum remained intact (arrow in A), but at the core of the injury, the corpus callosum was completely transected (arrow in B). Bar = 1 mm.
FIG. 2.
FIG. 2.
NAA concentrations in the injured hemisphere 4 and 6 days after injury, with and without GTA treatment. Statistical analysis was carried out using one-way ANOVA and Tukey's post-hoc test by HSD multiple comparisons (n = 8 for 4 days, n = 14 for 6 days). aValues (mean ± SEM) of the uninjured (control) group are compared to those of injured groups (p < 0.001). bValues (mean ± SEM) of water-treated injured group are compared to those of GTA-treated injured group (p < 0.001).
FIG. 3.
FIG. 3.
Percent change in ATP concentrations in the injured hemisphere 4 and 6 days after injury with and without GTA treatment. Statistical analysis was carried out using one-way ANOVA and Tukey's post-hoc test by HSD multiple comparisons (n = 8 for 4 days, and n = 14 for 6 days). aValues (% control ± SEM) of uninjured (control) group are compared to those of injured groups (p < 0.001). bValues (% control ± SEM) of water treated injured group are compared to those of GTA treated injured group (p < 0.001).
FIG. 4.
FIG. 4.
Rotarod performance 1, 3, and 5 days after CCI injury with and without GTA treatment. Statistical analysis was carried out using one-way ANOVA and Tukey's post-hoc test by HSD multiple comparisons (n = 14 per group). aValues (means ± SEM) of uninjured (control) group are compared to those of injured groups (p < 0.01). bValues (means ± SEM) of water-treated injured group are compared to those of GTA-treated injured group (p < 0.01).
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References

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