Is xenon combined with cooling an effective treatment for traumatic brain injury?

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Head Injury (Traumatic Brain Injury) is the most common cause of death and disability in children and adults under 40 in the UK, with car accidents and falls being the leading causes. In England & Wales approximately 1.4 million patients each year attend hospital Accident & Emergency departments with a head injury, and 200,000 are admitted as in-patients each year. There are no clinically-proven drug treatments that prevent brain cell loss after Head Injury. Clinical practice in Head Injury patients is largely supportive, centred on non-specific endpoints and management of physiological parameters (cerebral perfusion pressure, intracranial pressure(ICP) and tissue oxygenation). Head Injury is characterised by a "primary injury" from the mechanical insult, followed by "secondary injury" developing minutes, hours and days later. The majority of the neurological and cognitive deficits suffered by TBI patients result from potentially preventable secondary injury. There is an urgent need to develop drugs or combinations of treatments to prevent secondary injury after TBI and improve outcomes. Xenon is a gas that is currently used medically as a general anaesthetic. Our laboratory has been investigating the potential of xenon as a treatment that can prevent or limit the amount of brain damage that occurs after a Head Injury. We have recently shown that xenon, if given within 3 hours of injury, can limit the secondary brain injury and improve outcome in a rodent model of Head Injury. Cooling of the brain or the body is used for some types of brain injury (babies suffering from hypoxia) and in cardiac arrest patients. In this project we will determine whether cooling combined with xenon is more effective than xenon alone and whether cooling reduces the duration of treatment required or increases the time window within which xenon treatment is effective. The overall aim of this work is to develop xenon and cooling as a treatment for Head Injury patients. Xenon and cooling treatment could be given at the scene of injury, in the ambulance and later in the intensive care unit. Before the treatment could be used in patients it is first necessary to show a proof-of-concept that it works in an animal model of Head Injury. This project aims to obtain high quality pre-clinical data on the efficacy, the optimum xenon dose, temperature and the timing of the xenon and cooling treatment. This data will be essential in developing treatment strategies in future clinical trials of xenon and cooling in Head Injury. If xenon and cooling are effective it could be a simple treatment that could easily be given to Head Injury patients to improve their outcome and minimise long-term disability. These findings could bring benefit to Head Injury patients in terms of improved treatments and quality of life and could benefit the National Health Service in terms of reductions in the costs of treating long term disability.