Nutrition Therapy, Glucose Control, and Brain Metabolism in Traumatic Brain Injury: A Multimodal Monitoring Approach

Abstract

The goal of neurocritical care in patients with traumatic brain injury (TBI) is to prevent secondary brain damage. Pathophysiological mechanisms lead to loss of body mass, negative nitrogen balance, dysglycemia, and cerebral metabolic dysfunction. All of these complications have been shown to impact outcomes. Therapeutic options are available that prevent or mitigate their negative impact. Nutrition therapy, glucose control, and multimodality monitoring with cerebral microdialysis (CMD) can be applied as an integrated approach to optimize systemic immune and organ function as well as adequate substrate delivery to the brain. CMD allows real-time bedside monitoring of aspects of brain energy metabolism, by measuring specific metabolites in the extracellular fluid of brain tissue. Sequential monitoring of brain glucose and lactate/pyruvate ratio may reveal pathologic processes that lead to imbalances in supply and demand. Early recognition of these patterns may help individualize cerebral perfusion targets and systemic glucose control following TBI. In this direction, recent consensus statements have provided guidelines and recommendations for CMD applications in neurocritical care. In this review, we summarize data from clinical research on patients with severe TBI focused on a multimodal approach to evaluate aspects of nutrition therapy, such as timing and route; aspects of systemic glucose management, such as intensive vs. moderate control; and finally, aspects of cerebral metabolism. Research and clinical applications of CMD to better understand the interplay between substrate supply, glycemic variations, insulin therapy, and their effects on the brain metabolic profile were also reviewed. Novel mechanistic hypotheses in the interpretation of brain biomarkers were also discussed. Finally, we offer an integrated approach that includes nutritional and brain metabolic monitoring to manage severe TBI patients.

Keywords: brain glucose; cerebral microdialysis; glucose control; neurointensive care; nutrition therapy.

FIGURE 1

Outline of the pathway of eicosanoid synthesis from arachidonic acid. COX, cyclooxygenase; HETE, hydroxieicosatetraenoic; HpETE, hydroxiperoxyeicosatetraenoic; LOX, lipoxygenase; LT, leukotriene; PG, prostaglandin; TX, thromboxane.

FIGURE 2

Outline of the pathway of synthesis of Resolvins and related mediators from EPA and DHA. COX, cyclooxygenase; HpDHA, hydroxiperoxidocosahexaenoic; HpEPE, hydroxiperoxyeicosapentaenoic; LOX, lipoxygenase; LT, leucotriene; PG, prostaglandin; Rv, resolvin, TX, tromboxane.

FIGURE 3

Glucose metabolism. Glucose is first phosphorylated to glucose-6-phosphate (glucose-6-P), which has three fates that correspond to the three main functions of glucose. First, energy can be stored as glycogen. Glycogen can later be mobilized and subsequently metabolized to pyruvate. Second, energy in the form of ATP can be produced by glucose-6-P entering glycolysis, supplying pyruvate for the tricarboxylic acid (TCA) cycle in the mitochondria and the associated oxidative phosphorylation. Glycolysis produces ATP and NADH. Depending on the cell type, pyruvate can also be converted into lactate through the action of lactate dehydrogenase (LDH). Third, reducing equivalents in the form of NADPH are produced in the pentose phosphate pathway (PPP).

FIGURE 4

Glucose metabolism in the brain. The expression of different metabolic pathways for glucose is cell specific. Red arrows show upregulated pathways and black dashed arrows show downregulated pathways. Lactate production characterize astrocytes, whereas neurons use a significant proportion of glucose in the PPP (Bouzier-Sore and Bolanos, 2015) and use lactate, after its conversion to pyruvate, as their preferred mitochondrial energy substrate (Patet et al., 2016; Magistretti and Allaman, 2018). In summary, these cell-specific expression and activity profiles confer to neurons a restricted potential for upregulating glycolysis and an active oxidative phosphorylation activity. By contrast, in astrocytes, aerobic glycolysis is favored and oxidative activity is limited.