Cerebral Lactate Metabolism After Traumatic Brain Injury
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Cerebral energy dysfunction has emerged as an important determinant of prognosis following traumatic brain injury (TBI). A number of studies using cerebral microdialysis, positron emission tomography, and jugular bulb oximetry to explore cerebral metabolism in patients with TBI have demonstrated a critical decrease in the availability of the main energy substrate of brain cells (i.e., glucose). Energy dysfunction induces adaptations of cerebral metabolism that include the utilization of alternative energy resources that the brain constitutively has, such as lactate. Two decades of experimental and human investigations have convincingly shown that lactate stands as a major actor of cerebral metabolism. Glutamate-induced activation of glycolysis stimulates lactate production from glucose in astrocytes, with subsequent lactate transfer to neurons (astrocyte-neuron lactate shuttle). Lactate is not only used as an extra energy substrate but also acts as a signaling molecule and regulator of systemic and brain glucose use in the cerebral circulation. In animal models of brain injury (e.g., TBI, stroke), supplementation with exogenous lactate exerts significant neuroprotection. Here, we summarize the main clinical studies showing the pivotal role of lactate and cerebral lactate metabolism after TBI. We also review pilot interventional studies that examined exogenous lactate supplementation in patients with TBI and found hypertonic lactate infusions had several beneficial properties on the injured brain, including decrease of brain edema, improvement of neuroenergetics via a “cerebral glucose-sparing effect,” and increase of cerebral blood flow. Hypertonic lactate represents a promising area of therapeutic investigation; however, larger studies are needed to further examine mechanisms of action and impact on outcome.
KeywordsCerebral metabolism Energetic dysfunction Glucose Lactate Traumatic brain injury
Mauro Oddo is supported by research grants from the Swiss National Science Foundation (Grant no. 32003B_155957) and the Novartis Foundation for Biomedical Research.
Compliance with Ethical Standards
Conflict of Interest
Camille Patet, Tamarah Suys, Laurent Carteron, and Mauro Oddo have received payments to their institution from the Swiss National Science Foundation and the Novartis Foundation of Biomedical Research.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
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