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

氙气结合冷却是治疗脑外伤的有效方法吗？

• 批准号: MR/N027736/1
• 负责人: Robert Dickinson
• 金额: $ 78.53万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN027736%2F1
• 关键词: xenon; combined; cooling; effective; treatment

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.

头部受伤（脑外伤）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 万名头部受伤患者到医院急诊科就诊，每年有 20 万名患者住院。没有经过临床证明的药物治疗可以防止头部受伤后脑细胞损失。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。头部损伤的特点是机械损伤造成的“原发性损伤”，几分钟、几小时和几天后出现“继发性损伤”。 TBI 患者遭受的大多数神经和认知缺陷都是由可能可预防的继发性损伤造成的。迫切需要开发药物或治疗组合来预防 TBI 后的继发性损伤并改善预后。氙气是一种目前在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气作为一种治疗方法的潜力，可以预防或限制头部受伤后发生的脑损伤。我们最近表明，如果在受伤后 3 小时内给予氙气，可以限制继发性脑损伤并改善啮齿动物头部损伤模型的结果。大脑或身体冷却可用于治疗某些类型的脑损伤（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，以及冷却是否会缩短所需的治疗持续时间或增加氙气治疗有效的时间窗口。这项工作的总体目标是开发氙气和冷却技术来治疗头部受伤患者。可以在受伤现场、救护车上以及随后在重症监护室中进行氙气和冷却治疗。在将这种疗法用于患者之前，首先需要证明它在头部损伤动物模型中有效。该项目旨在获得有关疗效、最佳氙气剂量、温度以及氙气和冷却治疗时间的高质量临床前数据。这些数据对于制定未来氙气和头部损伤冷却临床试验的治疗策略至关重要。如果氙气和冷却有效，这可能是一种简单的治疗方法，可以很容易地对头部受伤患者进行治疗，以改善他们的治疗结果并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受伤患者带来好处，并可以在降低治疗长期残疾的成本方面使国家卫生服务受益。

项目成果

Xenon prevents early neuronal loss and neuroinflammation in a rat model of traumatic brain injury

氙可预防大鼠脑外伤模型的早期神经元丢失和神经炎症

• DOI: 10.1016/j.bja.2019.04.033
• 发表时间: 2019
• 期刊: British Journal of Anaesthesia
• 影响因子: 9.8
• 作者: Campos-Pires R

Xenon is neuroprotective against blast traumatic brain injury in vitro

氙对体外爆炸性脑损伤具有神经保护作用

• DOI: 10.1016/j.bja.2018.05.025
• 发表时间: 2018
• 期刊: British Journal of Anaesthesia
• 影响因子: 9.8
• 作者: Campos-Pires R

Xenon Protects against Blast-Induced Traumatic Brain Injury in an In Vitro Model.

• DOI: 10.1089/neu.2017.5360
• 发表时间: 2018-04-15
• 期刊: Journal of neurotrauma
• 影响因子: 4.2
• 作者: Campos-Pires R;Koziakova M;Yonis A;Pau A;Macdonald W;Harris K;Edge CJ;Franks NP;Mahoney PF;Dickinson R
• 通讯作者: Dickinson R

Xenon Treatment Prevents Late Onset Cognitive Impairment and Improves Survival Following Traumatic Brain Injury in Mice

氙气治疗可预防小鼠迟发性认知障碍并提高脑外伤后的存活率

• 发表时间: 2019
• 期刊: BRAIN INJURY
• 影响因子: 1.9
• 作者: Campos-Pires Rita

Xenon treatment improves short-term and long-term outcomes in a rodent model of traumatic brain injury

氙气治疗可改善创伤性脑损伤啮齿动物模型的短期和长期结果

• DOI: 10.1016/j.bja.2018.05.022
• 发表时间: 2018
• 期刊: British Journal of Anaesthesia
• 影响因子: 9.8
• 作者: Campos-Pires R