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Cerebral metabolism following traumatic brain injury: new discoveries with implications for treatment.

Brooks GA, Martin NA - Front Neurosci (2015)

Bottom Line: By tracking the incorporation of the (13)C from lactate tracer we found that gluconeogenesis (GNG) from lactate accounted for 67.1 ± 6.9%, of whole-body glucose appearance rate (Ra) in TBI, which was compared to 15.2 ± 2.8% (mean ± SD, respectively) in healthy, well-nourished controls.In particular, the advantages of using inorganic and organic lactate salts, esters and other compounds are examined.To date, several investigations on brain-injured patients with intact hepatic and renal functions show that compared to dextrose + insulin treatment, exogenous lactate infusion results in normal glycemia.

View Article: PubMed Central - PubMed

Affiliation: Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley Berkeley, CA, USA.

ABSTRACT
Because it is the product of glycolysis and main substrate for mitochondrial respiration, lactate is the central metabolic intermediate in cerebral energy substrate delivery. Our recent studies on healthy controls and patients following traumatic brain injury (TBI) using [6,6-(2)H2]glucose and [3-(13)C]lactate, along with cerebral blood flow (CBF) and arterial-venous (jugular bulb) difference measurements for oxygen, metabolite levels, isotopic enrichments and (13)CO2 show a massive and previously unrecognized mobilization of lactate from corporeal (muscle, skin, and other) glycogen reserves in TBI patients who were studied 5.7 ± 2.2 days after injury at which time brain oxygen consumption and glucose uptake (CMRO2 and CMRgluc, respectively) were depressed. By tracking the incorporation of the (13)C from lactate tracer we found that gluconeogenesis (GNG) from lactate accounted for 67.1 ± 6.9%, of whole-body glucose appearance rate (Ra) in TBI, which was compared to 15.2 ± 2.8% (mean ± SD, respectively) in healthy, well-nourished controls. Standard of care treatment of TBI patients in state-of-the-art facilities by talented and dedicated heath care professionals reveals presence of a catabolic Body Energy State (BES). Results are interpreted to mean that additional nutritive support is required to fuel the body and brain following TBI. Use of a diagnostic to monitor BES to provide health care professionals with actionable data in providing nutritive formulations to fuel the body and brain and achieve exquisite glycemic control are discussed. In particular, the advantages of using inorganic and organic lactate salts, esters and other compounds are examined. To date, several investigations on brain-injured patients with intact hepatic and renal functions show that compared to dextrose + insulin treatment, exogenous lactate infusion results in normal glycemia.

No MeSH data available.


Related in: MedlinePlus

Cerebral lactate Oxidation in control and TBI patients. Values given in relative terms (% lactate uptake that is oxidized). Lactate taken up by healthy controls and TBI patients is oxidized directly within the tissue. Values corrected for the contribution to cerebral release of 13CO2 from the oxidation of 13C-glucose produced from circulating [3-13C]lactate. From (Glenn et al., 2015).
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Figure 10: Cerebral lactate Oxidation in control and TBI patients. Values given in relative terms (% lactate uptake that is oxidized). Lactate taken up by healthy controls and TBI patients is oxidized directly within the tissue. Values corrected for the contribution to cerebral release of 13CO2 from the oxidation of 13C-glucose produced from circulating [3-13C]lactate. From (Glenn et al., 2015).

Mentions: Based on measurements of cerebral tracer-measured lactate uptake (TMU) (Figure 8B) and simultaneously measured 13CO2 excretion into the jugular bulb, cerebral lactate oxidation is essentially 100% (Figure 10). Among various things the data indicate that lactate entering the brains of healthy controls and TBI patients is not simply stored, but utilized as a fuel energy source. Importantly, the results (Figure 11) show that the brain oxidizes lactate directly, which is supported by evidence of the mLOC being present in the only species (rat) examined to date (Hashimoto et al., 2008).


Cerebral metabolism following traumatic brain injury: new discoveries with implications for treatment.

Brooks GA, Martin NA - Front Neurosci (2015)

Cerebral lactate Oxidation in control and TBI patients. Values given in relative terms (% lactate uptake that is oxidized). Lactate taken up by healthy controls and TBI patients is oxidized directly within the tissue. Values corrected for the contribution to cerebral release of 13CO2 from the oxidation of 13C-glucose produced from circulating [3-13C]lactate. From (Glenn et al., 2015).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321351&req=5

Figure 10: Cerebral lactate Oxidation in control and TBI patients. Values given in relative terms (% lactate uptake that is oxidized). Lactate taken up by healthy controls and TBI patients is oxidized directly within the tissue. Values corrected for the contribution to cerebral release of 13CO2 from the oxidation of 13C-glucose produced from circulating [3-13C]lactate. From (Glenn et al., 2015).
Mentions: Based on measurements of cerebral tracer-measured lactate uptake (TMU) (Figure 8B) and simultaneously measured 13CO2 excretion into the jugular bulb, cerebral lactate oxidation is essentially 100% (Figure 10). Among various things the data indicate that lactate entering the brains of healthy controls and TBI patients is not simply stored, but utilized as a fuel energy source. Importantly, the results (Figure 11) show that the brain oxidizes lactate directly, which is supported by evidence of the mLOC being present in the only species (rat) examined to date (Hashimoto et al., 2008).

Bottom Line: By tracking the incorporation of the (13)C from lactate tracer we found that gluconeogenesis (GNG) from lactate accounted for 67.1 ± 6.9%, of whole-body glucose appearance rate (Ra) in TBI, which was compared to 15.2 ± 2.8% (mean ± SD, respectively) in healthy, well-nourished controls.In particular, the advantages of using inorganic and organic lactate salts, esters and other compounds are examined.To date, several investigations on brain-injured patients with intact hepatic and renal functions show that compared to dextrose + insulin treatment, exogenous lactate infusion results in normal glycemia.

View Article: PubMed Central - PubMed

Affiliation: Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley Berkeley, CA, USA.

ABSTRACT
Because it is the product of glycolysis and main substrate for mitochondrial respiration, lactate is the central metabolic intermediate in cerebral energy substrate delivery. Our recent studies on healthy controls and patients following traumatic brain injury (TBI) using [6,6-(2)H2]glucose and [3-(13)C]lactate, along with cerebral blood flow (CBF) and arterial-venous (jugular bulb) difference measurements for oxygen, metabolite levels, isotopic enrichments and (13)CO2 show a massive and previously unrecognized mobilization of lactate from corporeal (muscle, skin, and other) glycogen reserves in TBI patients who were studied 5.7 ± 2.2 days after injury at which time brain oxygen consumption and glucose uptake (CMRO2 and CMRgluc, respectively) were depressed. By tracking the incorporation of the (13)C from lactate tracer we found that gluconeogenesis (GNG) from lactate accounted for 67.1 ± 6.9%, of whole-body glucose appearance rate (Ra) in TBI, which was compared to 15.2 ± 2.8% (mean ± SD, respectively) in healthy, well-nourished controls. Standard of care treatment of TBI patients in state-of-the-art facilities by talented and dedicated heath care professionals reveals presence of a catabolic Body Energy State (BES). Results are interpreted to mean that additional nutritive support is required to fuel the body and brain following TBI. Use of a diagnostic to monitor BES to provide health care professionals with actionable data in providing nutritive formulations to fuel the body and brain and achieve exquisite glycemic control are discussed. In particular, the advantages of using inorganic and organic lactate salts, esters and other compounds are examined. To date, several investigations on brain-injured patients with intact hepatic and renal functions show that compared to dextrose + insulin treatment, exogenous lactate infusion results in normal glycemia.

No MeSH data available.


Related in: MedlinePlus