Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Feb 21;25(5):2513.
doi: 10.3390/ijms25052513.

Cerebral Glucose Metabolism following TBI: Changes in Plasma Glucose, Glucose Transport and Alternative Pathways of Glycolysis-A Translational Narrative Review

Annerixt Gribnau  1 , Mark L van Zuylen  1   2 , Jonathan P Coles  3 , Mark P Plummer  4 , Henning Hermanns  1 , Jeroen Hermanides  1
Affiliations
Review

Cerebral Glucose Metabolism following TBI: Changes in Plasma Glucose, Glucose Transport and Alternative Pathways of Glycolysis-A Translational Narrative Review

Annerixt Gribnau et al. Int J Mol Sci. .

Abstract

Traumatic brain injury (TBI) is a major public health concern with significant consequences across various domains. Following the primary event, secondary injuries compound the outcome after TBI, with disrupted glucose metabolism emerging as a relevant factor. This narrative review summarises the existing literature on post-TBI alterations in glucose metabolism. After TBI, the brain undergoes dynamic changes in brain glucose transport, including alterations in glucose transporters and kinetics, and disruptions in the blood-brain barrier (BBB). In addition, cerebral glucose metabolism transitions from a phase of hyperglycolysis to hypometabolism, with upregulation of alternative pathways of glycolysis. Future research should further explore optimal, and possibly personalised, glycaemic control targets in TBI patients, with GLP-1 analogues as promising therapeutic candidates. Furthermore, a more fundamental understanding of alterations in the activation of various pathways, such as the polyol and lactate pathway, could hold the key to improving outcomes following TBI.

Keywords: cerebral glucose metabolism; hyperglycaemia; traumatic brain injury.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic summary of cerebral glucose metabolism in the healthy brain. Abbreviations: GLUT, glucose transporter; GP, glycogen phosphorylase; GS, glycogen synthase; HK, hexokinase; LDH, lactate dehydrogenase; MCT, monocarboxylate transporter; PDH, pyruvate dehydrogenase.
Figure 2
Figure 2
Michaelis–Menten kinetics. As substrate concentration rises the reaction rate increases until it approaches the maximum reaction rate (Vmax). The Michaelis–Menten constant (Km) is defined as the substrate concentration at which the reaction rate is half of Vmax.
Figure 3
Figure 3
Schematic representation of reversible Michaelis–Menten kinetics in brain compartments. After TBI, a decrease is seen in the injured area (2) in k1 and k3 compared to the healthy brain (1). In the uninjured area after TBI (3), only a decrease in k3 is seen. Figure based on measurements by Hattori et al. [68]. k1 represents transport of glucose into the brain by glucose transporters, whereas k3 represents hexokinase activity.
Figure 4
Figure 4
Polyol pathway. Abbreviations: AD, aldose reductase; HK, hexokinase; SDH, sorbitol dehydrogenase.
See this image and copyright information in PMC

References

    1. Global Burden of Disease 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18:56–87. doi: 10.1016/S1474-4422(18)30415-0. - DOI - PMC - PubMed
    1. Taylor C.A., Bell J.M., Breiding M.J., Xu L. Traumatic Brain Injury-Related Emergency Department Visits, Hospitalizations, and Deaths—United States, 2007 and 2013. MMWR Surveill. Summ. 2017;66:1–16. doi: 10.15585/mmwr.ss6609a1. - DOI - PMC - PubMed
    1. Clark D., Joannides A., Adeleye A.O., Bajamal A.H., Bashford T., Biluts H., Budohoski K., Ercole A., Fernandez-Mendez R., Figaji A., et al. Casemix, management, and mortality of patients rreseceiving emergency neurosurgery for traumatic brain injury in the Global Neurotrauma Outcomes Study: A prospective observational cohort study. Lancet Neurol. 2022;21:438–449. doi: 10.1016/S1474-4422(22)00037-0. - DOI - PubMed
    1. Dijkland S.A., Helmrich I., Nieboer D., van der Jagt M., Dippel D.W.J., Menon D.K., Stocchetti N., Maas A.I.R., Lingsma H.F., Steyerberg E.W., 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. doi: 10.1089/neu.2020.7300. - DOI - PubMed
    1. Stocchetti N., Zanier E.R. Chronic impact of traumatic brain injury on outcome and quality of life: A narrative review. Crit. Care. 2016;20:148. doi: 10.1186/s13054-016-1318-1. - DOI - PMC - PubMed