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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 rate (CMR) for chemical lactate [CMRlac = (CBF) (a-v)lac] over time in patients with severe TBI. To illustrate the change in CMRlac over time, data presented as percentage of patients demonstrating net cerebral lactate uptake (i.e., CMRlac < 0, white area) compared percentage of patients demonstrating cerebral net lactate release (i.e., CMRlac > 0, dark area). Patients display wide variability and significant changes over time with regression to control values of net cerebral lactate release over time. As illustrated in Figure 1, CMRlac underestimates total lactate production. Redrawn from Glenn et al. (2003) and ongoing studies with control values courtesy of T. C. Glenn.
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Figure 2: Cerebral metabolic rate (CMR) for chemical lactate [CMRlac = (CBF) (a-v)lac] over time in patients with severe TBI. To illustrate the change in CMRlac over time, data presented as percentage of patients demonstrating net cerebral lactate uptake (i.e., CMRlac < 0, white area) compared percentage of patients demonstrating cerebral net lactate release (i.e., CMRlac > 0, dark area). Patients display wide variability and significant changes over time with regression to control values of net cerebral lactate release over time. As illustrated in Figure 1, CMRlac underestimates total lactate production. Redrawn from Glenn et al. (2003) and ongoing studies with control values courtesy of T. C. Glenn.

Mentions: Science is difficult enough, and in the case of lactate metabolism understanding is complicated by the use of different terms in different fields. Hence, we need to define terms as they appear in this review. For brain, cerebral metabolic rate for glucose (CMRgluc) equals the arterial-venous difference for glucose (i.e., [a-v]gluc) times CBF: CMRgluc = (AVDgluc) (CBF). Similarly, for lactate (CMRlac) equals the arterial-venous difference ([a-v]lac) times CBF: CMRlac = (AVDlac) (CBF). As already noted, in skeletal (Stanley et al., 1986; Bergman et al., 1999b) and cardiac muscle (Gertz et al., 1988; Bergman et al., 2009), and lung (Johnson et al., 2012) physiology, the term net lactate exchange is equivalent to CMRlac and in these instances the negative sign (−) indicates net lactate release, whereas a positive sign (+) indicates net lactate uptake. For Figure 2 on cerebral net lactate exchange (>0 sign, and dark area) indicates net cerebral lactate release, whereas the (<0) sign and light area indicates lactate uptake as shown for control subjects and patients after suffering traumatic brain injury (TBI). In the first days following injury most patients display net cerebral lactate uptake transitioning to net release as in controls after several days of intensive care. This said, whether positive or negative, the CMR for lactate underestimates production because of simultaneous production and removal within brain tissue (van Hall et al., 2009; Glenn et al., 2015) as it does in other tissues such as skeletal muscle (Stanley et al., 1986; Bergman et al., 1999b) and heart (Gertz et al., 1988).


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

Brooks GA, Martin NA - Front Neurosci (2015)

Cerebral metabolic rate (CMR) for chemical lactate [CMRlac = (CBF) (a-v)lac] over time in patients with severe TBI. To illustrate the change in CMRlac over time, data presented as percentage of patients demonstrating net cerebral lactate uptake (i.e., CMRlac < 0, white area) compared percentage of patients demonstrating cerebral net lactate release (i.e., CMRlac > 0, dark area). Patients display wide variability and significant changes over time with regression to control values of net cerebral lactate release over time. As illustrated in Figure 1, CMRlac underestimates total lactate production. Redrawn from Glenn et al. (2003) and ongoing studies with control values courtesy of T. C. Glenn.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Cerebral metabolic rate (CMR) for chemical lactate [CMRlac = (CBF) (a-v)lac] over time in patients with severe TBI. To illustrate the change in CMRlac over time, data presented as percentage of patients demonstrating net cerebral lactate uptake (i.e., CMRlac < 0, white area) compared percentage of patients demonstrating cerebral net lactate release (i.e., CMRlac > 0, dark area). Patients display wide variability and significant changes over time with regression to control values of net cerebral lactate release over time. As illustrated in Figure 1, CMRlac underestimates total lactate production. Redrawn from Glenn et al. (2003) and ongoing studies with control values courtesy of T. C. Glenn.
Mentions: Science is difficult enough, and in the case of lactate metabolism understanding is complicated by the use of different terms in different fields. Hence, we need to define terms as they appear in this review. For brain, cerebral metabolic rate for glucose (CMRgluc) equals the arterial-venous difference for glucose (i.e., [a-v]gluc) times CBF: CMRgluc = (AVDgluc) (CBF). Similarly, for lactate (CMRlac) equals the arterial-venous difference ([a-v]lac) times CBF: CMRlac = (AVDlac) (CBF). As already noted, in skeletal (Stanley et al., 1986; Bergman et al., 1999b) and cardiac muscle (Gertz et al., 1988; Bergman et al., 2009), and lung (Johnson et al., 2012) physiology, the term net lactate exchange is equivalent to CMRlac and in these instances the negative sign (−) indicates net lactate release, whereas a positive sign (+) indicates net lactate uptake. For Figure 2 on cerebral net lactate exchange (>0 sign, and dark area) indicates net cerebral lactate release, whereas the (<0) sign and light area indicates lactate uptake as shown for control subjects and patients after suffering traumatic brain injury (TBI). In the first days following injury most patients display net cerebral lactate uptake transitioning to net release as in controls after several days of intensive care. This said, whether positive or negative, the CMR for lactate underestimates production because of simultaneous production and removal within brain tissue (van Hall et al., 2009; Glenn et al., 2015) as it does in other tissues such as skeletal muscle (Stanley et al., 1986; Bergman et al., 1999b) and heart (Gertz et al., 1988).

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