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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

Components of cerebral lactate metabolism: Release (CMRlac), Tracer-Measured Uptake and Total Cerebral Lactate Production = TMU-CMRlac. Solid lines represent TBI patients while dashed lines are normal control subjects. The use of [13-13C]lactate tracer allow a very different view of cerebral lact production. Should CMRlac be taken as a measure of lactate production, total lactate production would be grossly underestimated. Regardless, whether estimated from CMR or total lactate production, control subjects and TBI patients show similar capacities for lactate uptake, release and production. From Glenn et al. (2015).
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Figure 9: Components of cerebral lactate metabolism: Release (CMRlac), Tracer-Measured Uptake and Total Cerebral Lactate Production = TMU-CMRlac. Solid lines represent TBI patients while dashed lines are normal control subjects. The use of [13-13C]lactate tracer allow a very different view of cerebral lact production. Should CMRlac be taken as a measure of lactate production, total lactate production would be grossly underestimated. Regardless, whether estimated from CMR or total lactate production, control subjects and TBI patients show similar capacities for lactate uptake, release and production. From Glenn et al. (2015).

Mentions: Figure 8A shows cerebral lactate fractional exaction (FExlac) to approximate 10% in both healthy control subjects and those suffering TBI (Glenn et al., 2015). Incidentally, the FEx for glucose also approximates 10% in healthy subjects and TBI patients (Glenn et al., 2015), so the value of 10% FEx for lactate is in the range of biological plausibility. Nonetheless, knowing CBF, arterial [lactate] and FExlac, cerebral tracer-measured lactate uptake (TMUlac) can be determined and compared to 13CO2 excretion. With our moderate and severe TBI patients studied 5.7 ± 2.2 days after injury tracer-measured cerebral lactate uptake was not different from values measured in healthy control subjects (Figure 8B). Then, knowing and summing net lactate release (CMRlac) and cerebral tracer-measured lactate uptake (TMUlac), total cerebral lactate production can be determined (Figure 9). As shown in Figure 9, the conceptual model of cerebral lactate metabolism developed from seeing concentration-based depictions, such as arterial [glucose] and [lactate] (Figure 3), and CMRgluc and CMRlac (Figure 4), is very different from that developed from knowledge of total cerebral lactate production (Figure 9). To reiterate, new information of whole-body and cerebral glucose-lactate interactions show that glucose metabolism is suppressed following TBI, but lactate metabolism is intact. This knowledge provides impetus to explore the possibility of supporting cerebral carbohydrate metabolism and improving patient outcomes following injury by providing formulations containing lactate and other monocarboxylates.


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

Brooks GA, Martin NA - Front Neurosci (2015)

Components of cerebral lactate metabolism: Release (CMRlac), Tracer-Measured Uptake and Total Cerebral Lactate Production = TMU-CMRlac. Solid lines represent TBI patients while dashed lines are normal control subjects. The use of [13-13C]lactate tracer allow a very different view of cerebral lact production. Should CMRlac be taken as a measure of lactate production, total lactate production would be grossly underestimated. Regardless, whether estimated from CMR or total lactate production, control subjects and TBI patients show similar capacities for lactate uptake, release and production. From Glenn et al. (2015).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 9: Components of cerebral lactate metabolism: Release (CMRlac), Tracer-Measured Uptake and Total Cerebral Lactate Production = TMU-CMRlac. Solid lines represent TBI patients while dashed lines are normal control subjects. The use of [13-13C]lactate tracer allow a very different view of cerebral lact production. Should CMRlac be taken as a measure of lactate production, total lactate production would be grossly underestimated. Regardless, whether estimated from CMR or total lactate production, control subjects and TBI patients show similar capacities for lactate uptake, release and production. From Glenn et al. (2015).
Mentions: Figure 8A shows cerebral lactate fractional exaction (FExlac) to approximate 10% in both healthy control subjects and those suffering TBI (Glenn et al., 2015). Incidentally, the FEx for glucose also approximates 10% in healthy subjects and TBI patients (Glenn et al., 2015), so the value of 10% FEx for lactate is in the range of biological plausibility. Nonetheless, knowing CBF, arterial [lactate] and FExlac, cerebral tracer-measured lactate uptake (TMUlac) can be determined and compared to 13CO2 excretion. With our moderate and severe TBI patients studied 5.7 ± 2.2 days after injury tracer-measured cerebral lactate uptake was not different from values measured in healthy control subjects (Figure 8B). Then, knowing and summing net lactate release (CMRlac) and cerebral tracer-measured lactate uptake (TMUlac), total cerebral lactate production can be determined (Figure 9). As shown in Figure 9, the conceptual model of cerebral lactate metabolism developed from seeing concentration-based depictions, such as arterial [glucose] and [lactate] (Figure 3), and CMRgluc and CMRlac (Figure 4), is very different from that developed from knowledge of total cerebral lactate production (Figure 9). To reiterate, new information of whole-body and cerebral glucose-lactate interactions show that glucose metabolism is suppressed following TBI, but lactate metabolism is intact. This knowledge provides impetus to explore the possibility of supporting cerebral carbohydrate metabolism and improving patient outcomes following injury by providing formulations containing lactate and other monocarboxylates.

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