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

头部损伤（创伤性脑损伤）是英国40岁以下儿童和成人死亡和残疾的最常见原因，其中车祸和跌倒是主要原因。在英格兰和威尔士，每年约有140万名头部受伤的患者进入医院急诊科，每年有20万名住院患者。目前还没有临床证明的药物治疗可以防止脑损伤后的脑细胞损失。头部损伤患者的临床实践在很大程度上是支持性的，以非特异性终点和生理参数（脑灌注压、颅内压（ICP）和组织氧合）的管理为中心。头部损伤的特点是由机械损伤引起的“原发性损伤”，随后是几分钟、几小时和几天后发生的“继发性损伤”。大多数脑外伤患者的神经和认知功能缺陷是由潜在的可预防的继发性损伤引起的。迫切需要开发药物或联合治疗来预防脑外伤后的继发性损伤并改善预后。氙气是一种目前医学上用作全身麻醉剂的气体。我们的实验室一直在研究氙作为一种治疗方法的潜力，它可以预防或限制脑损伤后发生的脑损伤。我们最近在啮齿动物脑损伤模型中表明，如果在损伤后3小时内给予氙气，可以限制继发性脑损伤并改善预后。大脑或身体的冷却用于某些类型的脑损伤（婴儿缺氧）和心脏骤停患者。在这个项目中，我们将确定冷却与氙气结合是否比单独使用氙气更有效，以及冷却是否减少了所需治疗的持续时间或增加了氙气治疗有效的时间窗口。这项工作的总体目标是开发氙和冷却作为头部损伤患者的治疗方法。氙气和冷却治疗可以在受伤现场、救护车和随后的重症监护室进行。在治疗可以用于患者之前，首先有必要证明它在头部损伤的动物模型中有效。本项目旨在获得高质量的临床前数据，包括疗效、最佳氙气剂量、温度以及氙气和冷却治疗的时间。这一数据将是至关重要的，为制定治疗策略，在未来的临床试验氙气和冷却头部损伤。如果氙气和冷却是有效的，这可能是一个简单的治疗方法，可以很容易地给头部受伤的病人，以改善他们的结果，最大限度地减少长期残疾。这些发现可以在改善治疗和生活质量方面为头部损伤患者带来好处，并可以在减少治疗长期残疾的费用方面为国家卫生服务带来好处。

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.