New therapeutic strategies in the treatment of traumatic brain injury by targeting the LEctin Activation Pathway of complement

创伤性脑损伤（TBI）是由头部创伤（头部损伤）引起的脑损伤。TBI的主要原因是道路交通事故，袭击，福尔斯和家庭或工作中的事故。在英国，每年约有100万例头部受伤的病例出现在急诊室，其中15%需要住院治疗。TBI造成的损伤可能是暂时的或永久性的，导致不同程度的身体、认知和行为/情感障碍或死亡。TBI的结果由初始损伤的严重程度和损伤后炎症反应的程度决定。限制损伤后的炎症反应是一种理想的神经保护治疗，可以显着改善TBI的临床结果。该项目基于观察到先天免疫防御的一种定义的促炎途径，称为补体的凝集素激活途径，在损伤后驱动炎症中起着关键作用，研究人员已经确定了损伤后驱动这种炎症反应的关键酶。这种酶仅由肝细胞产生，并通过血液供应到达其他器官，在那里它以非常低的血浆水平存在。如先前在中风、心肌梗塞和肾移植的实验模型中所示，通过施用显著减少炎性组织损失的单克隆抗体，可以实现该酶的有效和持久的治疗消耗。实验TBI模型中的初步结果清楚地暗示MASP-2抑制将有效地限制创伤后炎症和CNS组织的损失。该项目可能提供推进新的高度神经保护性临床治疗所需的主要数据证明，以降低TBI后的发病率和死亡率。

Traumatic Brain Injury (TBI) is an injury to the brain caused by a trauma to the head (head injury). The main causes of TBI are road traffic accidents, assaults, falls and accidents at home or at work. An the UK, approximately 1 million cases with head injury are seen in Accident and Emergency Clinics per year of which 15% require hospitalisation. The damage caused by TBI can be temporary or permanent leading to various degrees of physical, cognitive, and behavioural/emotional impairments or death. The outcome of TBI is determined by the severity of the initial injury and by the degree of the inflammatory response following the injury. Limiting the inflammatory response following the injury is a desirable neuroprotective treatment that can significantly improve the clinical outcome of TBI. This project is based the observationthat a defined pro-inflammatory pathway of the innate immune defence, called the lectin activation pathway of complement, plays a key role in driving inflammation following injury and the investigators have identified the key enzyme that drives this inflammatory response following injury. This enzyme is exclusively made by liver cells and reaches other organs through the blood supply where it is present at very low plasma levels. An effective and long-lasting therapeutic depletion of this enzyme can be achieved by administration of a monoclonal antibody which significantly reduces inflammatory tissue loss as previously shown in experimental models of stroke, myocardial infarction and renal transplantation. The preliminary results in experimental TBI model clearly imply that MASP-2 inhibition will effectively limit post-traumatic inflammation and loss of CNS tissue. This project is likely to deliver the proof-of-principal data required to advance a new and highly neuroprotective clinical therapy to reduce morbidity and mortality following TBI.