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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 metabolic rates (CMR) for glucose (A) and lactate (B), in control and TBI patients; CMR = (Metabolite AVD) (Cerebral Blood Flow), alternatively termed net exchange. Values were constant over time, so mean values for min 60, 90, and 120 min are shown. Solid lines represent TBI patients (n = 12) while dashed lines are normal control subjects (n–6); other aspects of the figure described in the legend to Figure 3, above. Figures show net glucose uptake and net lactate release. Compared to values in controls, CMRgluc, but not CMRlac, was depressed in TBI patients. From Glenn et al. (2015).
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Figure 4: Cerebral metabolic rates (CMR) for glucose (A) and lactate (B), in control and TBI patients; CMR = (Metabolite AVD) (Cerebral Blood Flow), alternatively termed net exchange. Values were constant over time, so mean values for min 60, 90, and 120 min are shown. Solid lines represent TBI patients (n = 12) while dashed lines are normal control subjects (n–6); other aspects of the figure described in the legend to Figure 3, above. Figures show net glucose uptake and net lactate release. Compared to values in controls, CMRgluc, but not CMRlac, was depressed in TBI patients. From Glenn et al. (2015).

Mentions: Along the way to studying cerebral glucose-lactate interactions in patients following TBI an unexpected result emerged on our TBI patients given standard of care treatment in state of the art facilities by the dedicated and highly trained health care professionals. This was the herculean effort of the body to mobilize energy resources for the injured brain (Glenn et al., 2014). With reference Figure 2, patients were enrolled in our isotope tracer studies involving use of primed-continuous infusions of [6,6-2H2]glucose (i.e., D2-glucose) and [3-13C]lactate to track whole-body and cerebral glucose-lactate interactions in TBI. Patients were studied as soon as permission of legal representatives could be obtained, usually 96–140 h after injury at which time numerous parameters were approaching control levels. The time lag had to do with mechanics of securing permission of patients' legal representatives to conduct studies on patients receiving standard of care treatment. Consequently, at the time of study arterial glucose (Figure 3A) and lactate (Figure 3B) concentrations in patients were not significantly different from those in fasting control subjects. However, compared to values in control subjects, in TBI patients CMRgluc was significantly depressed (Figure 4A) (p < 0.01), whereas consistent with Figure 2 values, CMRlac was similar to control values (Figure 4B).


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

Brooks GA, Martin NA - Front Neurosci (2015)

Cerebral metabolic rates (CMR) for glucose (A) and lactate (B), in control and TBI patients; CMR = (Metabolite AVD) (Cerebral Blood Flow), alternatively termed net exchange. Values were constant over time, so mean values for min 60, 90, and 120 min are shown. Solid lines represent TBI patients (n = 12) while dashed lines are normal control subjects (n–6); other aspects of the figure described in the legend to Figure 3, above. Figures show net glucose uptake and net lactate release. Compared to values in controls, CMRgluc, but not CMRlac, was depressed in TBI patients. From Glenn et al. (2015).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Cerebral metabolic rates (CMR) for glucose (A) and lactate (B), in control and TBI patients; CMR = (Metabolite AVD) (Cerebral Blood Flow), alternatively termed net exchange. Values were constant over time, so mean values for min 60, 90, and 120 min are shown. Solid lines represent TBI patients (n = 12) while dashed lines are normal control subjects (n–6); other aspects of the figure described in the legend to Figure 3, above. Figures show net glucose uptake and net lactate release. Compared to values in controls, CMRgluc, but not CMRlac, was depressed in TBI patients. From Glenn et al. (2015).
Mentions: Along the way to studying cerebral glucose-lactate interactions in patients following TBI an unexpected result emerged on our TBI patients given standard of care treatment in state of the art facilities by the dedicated and highly trained health care professionals. This was the herculean effort of the body to mobilize energy resources for the injured brain (Glenn et al., 2014). With reference Figure 2, patients were enrolled in our isotope tracer studies involving use of primed-continuous infusions of [6,6-2H2]glucose (i.e., D2-glucose) and [3-13C]lactate to track whole-body and cerebral glucose-lactate interactions in TBI. Patients were studied as soon as permission of legal representatives could be obtained, usually 96–140 h after injury at which time numerous parameters were approaching control levels. The time lag had to do with mechanics of securing permission of patients' legal representatives to conduct studies on patients receiving standard of care treatment. Consequently, at the time of study arterial glucose (Figure 3A) and lactate (Figure 3B) concentrations in patients were not significantly different from those in fasting control subjects. However, compared to values in control subjects, in TBI patients CMRgluc was significantly depressed (Figure 4A) (p < 0.01), whereas consistent with Figure 2 values, CMRlac was similar to control values (Figure 4B).

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