AAGBI/Anaesthesia Research Fellowship
Mechanisms, spatial distribution and temporal pattern of energy failure following head injury
Dr Tonny Veenith
Background
Head injury is a common cause of death and disability, and has long been considered incurable by doctors and public alike. Over the past 30 years, remarkable advances in medical science have made many facets of this dreadful disease treatable. One achievement pioneered in the UK has been the development of the brain scanner, which can safely examine the inner structure and workings of the brain. The Wolfson Brain Imaging Centre is one of the few units worldwide having built an intensive
care unit for critically ill patients with brain disorders, in which one of the most powerful research scanners (MRI) has been included. Research using this scanner has already had some impact on the treatment provided, both when patients are first admitted, and when they are recovering from their illness.
Aims
Outcome following head injury has improved through the provision of high quality intensive care within specialised centres but further studies are desperately needed to understand why new therapies designed in laboratory do not always work in patients. This study will improve our understanding of the mechanisms responsible for energy production failure and cell loss in brain regions that survive the initial injury using non-invasive imaging within real patients. Why and when do different parts of the brain become damaged and die following injury? These studies offer the hope of identifying not only which new treatments should used, but when best to employ them.
Methodology
This study will observe sequential derangements in brain metabolism and other evidence of brain injury using MRI and spectroscopy in a group of 25 patients managed within the specialist intensive care unit at Addenbrooke's Hospital, Cambridge. MR Spectroscopy provides functional assessment of metabolism across the whole brain by quantifying various compounds including N-Acetylaspartate (NAA). NAA is a marker of normal energy metabolism within the power plants of cells (mitochondria), and is found in high concentrations within healthy brain cells. Although brain NAA
levels are decreased following head injury early changes may be reversible and amenable to therapy. Studies have suggested that brain metabolism is sensitive to local tissue oxygen levels, and the second part of this proposal will assess the impact of an increase in the percentage of inspired oxygen on brain metabolism and function during an interventional imaging study. All subjects will be reviewed at 6 - 12 months following injury where imaging will be repeated and recovery assessed.
Expected outcomes
Sequential measurements of NAA will address whether derangements are reversible and represent metabolic dysfunction, or irreversible and represent on going brain cell loss. The interventional study will assess whether an increase in the fraction of inspired oxygen can have a beneficial effect on regional energy metabolism and brain cell survival.
Implications
These data will improve understanding of the mechanisms responsible for energy production failure and cellular injury and detail when such injury occurs. This may provide important advances in the design and implementation of future drug based and clinical therapies aimed at preserving brain cells that survive the initial head injury.
