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Review
. 2022 Oct 1;35(5):562-569.
doi: 10.1097/ACO.0000000000001183. Epub 2022 Aug 18.

Cerebral metabolic derangements following traumatic brain injury

Simon Demers-Marcil  1   2 , Jonathan P Coles  1
Affiliations
Review

Cerebral metabolic derangements following traumatic brain injury

Simon Demers-Marcil et al. Curr Opin Anaesthesiol. .

Abstract

Purpose of review: Outcome following traumatic brain injury (TBI) remains variable, and derangements in cerebral metabolism are a common finding in patients with poor outcome. This review compares our understanding of cerebral metabolism in health with derangements seen following TBI.

Recent findings: Ischemia is common within the first 24 h of injury and inconsistently detected by bedside monitoring. Metabolic derangements can also result from tissue hypoxia in the absence of ischemic reductions in blood flow due to microvascular ischemia and mitochondrial dysfunction. Glucose delivery across the injured brain is dependent on blood glucose and regional cerebral blood flow, and is an important contributor to derangements in glucose metabolism. Alternative energy substrates such as lactate, ketone bodies and succinate that may support mitochondrial function, and can be utilized when glucose availability is low, have been studied following TBI but require further investigation.

Summary: Mitochondrial dysfunction and the use of alternative energy substrates are potential therapeutic targets, but improved understanding of the causes, impact and significance of metabolic derangements in clinical TBI are needed. Maintaining adequate oxygen and glucose delivery across the injured brain may accelerate the recovery of mitochondrial function and cerebral energy metabolism and remain important management targets.

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Conflict of interest statement

There are no conflicts of interest.

Figures

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FIGURE 1
FIGURE 1
Schematic to demonstrate derangements in glucose metabolism following traumatic brain injury. Cerebral blood flow (CBF), lactate dehydrogenase (LDH), mitochondrial respiratory chain (Mito resp chain), nicotinamide adenine dinucleotide and its reduced form (NAD and NADH), oxygen extraction fraction (OEF), partial pressure of oxygen (pO2), TCA (tricarboxylic acid cycle). Under normal conditions both glucose and lactate can be metabolized to pyruvate which enters the tricarboxylic acid cycle and undergoes oxidative phosphorylation. While the concentration of lactate is higher than that of pyruvate the lactate/pyruvate ratio remains less than 20 (a). In classical ischemia the increase in oxygen extraction fraction that results from a reduction in cerebral blood flow can no longer maintain oxygen delivery to the brain and tissue pO2 falls preventing mitochondrial oxidative phosphorylation. Pyruvate is converted to lactate via lactate dehydrogenase generating NAD which is required to maintain increased glycolysis and energy production, and the lactate/pyruvate ratio increases to levels more than 25 (b). A similar increase in glycolysis resulting in a lactate/pyruvate ratio more than 25 occurs in microvascular ischemia where microvascular thrombosis, collapse and perivascular edema result in an increased diffusion barrier that limits oxygen delivery leading to low tissue pO2 (c), and mitochondrial dysfunction where oxidative phosphorylation is suspended despite maintenance of normal oxygen and glucose delivery (d). In both (c) and (d), average macrovascular cerebral blood flow and oxygen extraction fraction values are not typically ischemic. Modified with permission from that originally published in Menon DK, Ercole A. Critical care management of traumatic brain injury. Handb Clin Neurol 2017;140:239–74.
FIGURE 2
FIGURE 2
Cerebral ischemia. Computed tomography, cerebral blood flow, cerebral metabolic rate of oxygen, oxygen extraction fraction, ischemic brain volume (IBV) and PET 18F-fluorodeoxyglucose kinetic parameters for K1 (glucose delivery) and k3 (glycolysis) obtained in a 40-year-old female within 24 h of severe traumatic brain injury resulting from a fall. The computed tomography scan was obtained following evacuation of a subdural hematoma and demonstrates residual subdural blood with minimal midline shift and underlying hemorrhagic contusions. Cerebral blood flow, cerebral metabolic rate of oxygen and (K1) glucose delivery are reduced, whereas oxygen extraction fraction and k3 (glycolysis) are increased within the hemisphere underlying the subdural. These findings are consistent with classical ischemia.
FIGURE 3
FIGURE 3
Glucose delivery and glycolysis are dependent on cerebral blood flow. The relationship between cerebral blood flow and 18F-fluorodeoxyglucose kinetic parameters for K1 (glucose delivery; left) and k3 (glycolysis; right) plotted for patients following traumatic brain injury. The fitted lines represent modeling of the relationship using locally weighted scatterplot smoothing, with the 95% confidence interval shown in gray. The vertical and horizontal dotted lines indicate the full range for healthy volunteer cerebral blood flow and 18F-fluorodeoxyglucose kinetic parameters, respectively.
FIGURE 4
FIGURE 4
Impact of low glucose delivery on glycolysis. The relationship between the proportion of glucose that undergoes glycolysis and glucose within brain tissue modeled using locally weighted scatterplot smoothing. Data shown are within lesion core (black), penumbra (light gray) and peri-penumbra (dark gray) regions following traumatic brain injury.
See this image and copyright information in PMC

References

    1. Dijkland SA, Helmrich I, Nieboer D, et al. . Outcome prediction after moderate and severe traumatic brain injury: external validation of two established prognostic models in 1742 European patients. J Neurotrauma 2021; 38:1377–1388. - PubMed
    1. Hoffman H, Abi-Aad K, Bunch KM, et al. . Outcomes associated with brain tissue oxygen monitoring in patients with severe traumatic brain injury undergoing intracranial pressure monitoring. J Neurosurg 2021; 135:1799–1806. - PubMed
    1. Guilfoyle MR, Helmy A, Donnelly J, et al. . Characterising the dynamics of cerebral metabolic dysfunction following traumatic brain injury: a microdialysis study in 619 patients. PLoS One 2021; 16:e0260291. - PMC - PubMed

    2. Large-scale retrospective study highlighting the prevalence of metabolic injuries shown on cerebral microdialysis and its association with neurological outcomes and various modifiable monitoring variables such as cerebral perfusion pressure, pressure reactivity index, PbtO2 and brain glucose. Threshold values associated with higher lactate/pyruvate ratio for these variables are identified which provides grounds for the selection of specific treatment targets.

    1. Launey Y, Fryer TD, Hong YT, et al. . Spatial and temporal pattern of ischemia and abnormal vascular function following traumatic brain injury. JAMA Neurol 2020; 77:339–349. - PMC - PubMed

    2. In-depth multitracer oxygen-15 PET study improving our understanding of macrovascular ischemia, both in the perilesional area and away from the area of visible injury. These changes were shown to be often undetectable by jugular bulb oximetry and brain tissue oxygen probes and sometimes present despite normal cerebral perfusion pressure and intracranial pressure.

    1. Hermanides J, Hong YT, Trivedi M, et al. . Metabolic derangements are associated with impaired glucose delivery following traumatic brain injury. Brain 2021; 144:3492–3504. - PMC - PubMed

    2. This cohort study used PET imaging to improve our understanding of changes in glucose metabolism following traumatic brain injury (TBI) and its relationship with ischemic brain. It identifies compensating mechanisms (upregulation of K1) to preserve glucose delivery in the setting of reduced cerebral blood flow and reveals targets for both plasma and cerebral glucose.