Dataset Information

The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury.

ABSTRACT: The postinjury period of glucose metabolic depression is accompanied by adenosine triphosphate decreases, increased flux of glucose through the pentose phosphate pathway, free radical production, activation of poly-ADP ribose polymerase via DNA damage, and inhibition of glyceraldehyde dehydrogenase (a key glycolytic enzyme) via depletion of the cytosolic NAD pool. Under these post-brain injury conditions of impaired glycolytic metabolism, glucose becomes a less favorable energy substrate. Ketone bodies are the only known natural alternative substrate to glucose for cerebral energy metabolism. While it has been demonstrated that other fuels (pyruvate, lactate, and acetyl-L-carnitine) can be metabolized by the brain, ketones are the only endogenous fuel that can contribute significantly to cerebral metabolism. Preclinical studies employing both pre- and postinjury implementation of the ketogenic diet have demonstrated improved structural and functional outcome in traumatic brain injury (TBI) models, mild TBI/concussion models, and spinal cord injury. Further clinical studies are required to determine the optimal method to induce cerebral ketone metabolism in the postinjury brain, and to validate the neuroprotective benefits of ketogenic therapy in humans.

SUBMITTER: Prins ML

PROVIDER: S-EPMC4242438 | biostudies-other | 2014 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury.

Prins Mayumi L ML Matsumoto Joyce H JH

Journal of lipid research 20140410 12

The postinjury period of glucose metabolic depression is accompanied by adenosine triphosphate decreases, increased flux of glucose through the pentose phosphate pathway, free radical production, activation of poly-ADP ribose polymerase via DNA damage, and inhibition of glyceraldehyde dehydrogenase (a key glycolytic enzyme) via depletion of the cytosolic NAD pool. Under these post-brain injury conditions of impaired glycolytic metabolism, glucose becomes a less favorable energy substrate. Ketone ...[more]

PMID: 24721741

Similar Datasets

Project description:BACKGROUND:Hyperventilation-induced hypocapnia (HV) reduces elevated intracranial pressure (ICP), a dangerous and potentially fatal complication of traumatic brain injury (TBI). HV decreases the arteriolar diameter of intracranial vessels, raising the risk of cerebral ischemia. The aim of this study was to characterize the effects of moderate short-term HV in patients with severe TBI by using concomitant monitoring of cerebral metabolism, brain tissue oxygen tension (PbrO2), and cerebral hemodynamics with transcranial color-coded duplex sonography (TCCD). METHODS:This prospective trial was conducted between May 2014 and May 2017 in the surgical intensive care unit (ICU) at the University Hospital of Zurich. Patients with nonpenetrating TBI older than 18 years of age with a Glasgow Coma Scale (GCS) score?<?9 at presentation and with ICP monitoring, PbrO2, and/or microdialysis (MD) probes during ICU admission within 36?h after injury were included in our study. Data collection and TCCD measurements were performed at baseline (A), at the beginning of moderate HV (C), after 50?min of moderate HV (D), and after return to baseline (E). Moderate HV was defined as arterial partial pressure of carbon dioxide 4-4.7?kPa. Repeated measures analysis of variance was used to compare variables at the different time points, followed by post hoc analysis with Bonferroni adjustment as appropriate. RESULTS:Eleven patients (64% males, mean age 36?±?14?years) with an initial median GCS score of 7 (IQR 3-8) were enrolled. During HV, ICP and mean flow velocity (CBFV) in the middle cerebral artery decreased significantly. Glucose, lactate, and pyruvate in the brain extracellular fluid did not change significantly, whereas PbrO2 showed a statistically significant reduction but remained within the normal range. CONCLUSION:Moderate short-term hyperventilation has a potent effect on the cerebral blood flow, as shown by TCCD, with a concomitant ICP reduction. Under the specific conditions of this study, this degree of hyperventilation did not induce pathological alterations of brain metabolites and oxygenation. TRIAL REGISTRATION:NCT03822026 . Registered on 30 January 2019.

Dataset Information

The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury.

Publications

The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets