GOMB-TBI · Causes and consequences of alterations in cerebral glucose metabolism in Traumatic Brain Injury
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-11-01 → 2016-10-31
- EU contribution
- €97,727
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Causes and consequences of alterations in cerebral glucose metabolism in Traumatic Brain Injury
Traumatic brain injury (TBI) is the leading cause of death and disability in young adults, although the incidence in the elderly is also increasing. It is estimated that around 7.7 million people are living with TBI related disability in the European Union alone. Derangements in cerebral glucose metabolism are common after traumatic brain injury (TBI). Although some of these metabolic changes can be attributed to a switch to anaerobic glycolysis in the presence of classical ischaemia, this is not the principal mechanism. Instead the underlying pathophysiology is more heterogenic and complex, as glucose metabolism depends on glucose delivery (blood flow), glucose uptake, finally phosphorylation and also glucose availability (plasma glucose). 18F-FDG Positron Emmision Tomography (PET) allows imaging of regional glucose metabolism and non-invasive assessment of the different kinetic glucose parameters. Combining this imaging technique with data from plasma glucose and interstitial brain glucose measured by microdialysis, allows assessemnt of the pathophysiology. Improving our understanding of the derangements in glucose metabolism after TBI may contribute to developing proper treatment to prevent secondary injury, which is key in improving outcome. The aim of this study therefore was to interrogate the underlying pathophysiological mechanisms responsible for such changes in cerebral glucose metabolism. Using combined 18F-fluorodeoxyglucose (18FDG) and oxygen-15 (15O) whole brain positron emission tomography (PET), the main objective is to study how derangements in 18FDG kinetic parameters relate to visible TBI lesions and changes in cerebral blood flow (CBF), oxygen metabolism (CMRO2), oxygen extraction fraction (OEF), plasma glucose and microdialysis glucose. Specific objectives 1) Investigate the relationship between oxygen and glucose metabolism in injured and non-injured brain regions after TBI using 15O and 18FDG PET imaging. 2) Investigate the relationship between plasma glucose, microdialysis glucose and cerebral glucose metabolism 3) Investigate the temporal evolution of alterations in cerebral metabolism using serial 15O and 18FDG PET.
Data: CORDIS, © European Union
Project objective
Traumatic Brain Injury (TBI) is the leading cause of death and disability in young adults. Hours or days after the primary injury, secondary injury will develop. This secondary injury is responsible for most in-hospital deaths after TBI. Early interventions to prevent secondary injury are currently targeted at reducing intracerebral pressure and promoting cerebral blood flow (CBF), aiming to improve brain oxygenation and reduce ischaemia. However, there is increasing evidence that other mechanisms besides ischaemia are important in the development of secondary damage. Because our brain depends on glucose for functioning, alterations in cerebral glucose metabolism provide insight into the causes of secondary brain damage. The influence of plasma glucose has been studied, but the relation between body and brain glucose metabolism after TBI is unclear. In addition, there are indications that local neuroinflammation influences local glucose metabolism. New techniques, such as positron emission tomography (PET) with 18-Fluorodeoxyglucose (18FDG) and cerebral microdialsyis, allow detailed study of brain metabolism after TBI. During this project we aim to study the causes and consequences of alterations in brain glucose metabolism using 18FDG PET and microdialysis. We will study the influence of alterations in oxygen supply, neuroinflammation and body glucose on alterations in glucose metabolism. Thereafter, the consequences of alterations in glucose metabolism on brain tissue will be studied, using structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). This will provide novel insights into the underlying mechanisms of secondary injury following TBI and its long term consequences. These data should provide a basis for the design and assessment of future neuroprotective therapies.
Original text from CORDIS.
Participants
- THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGECoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union