Cellular Neuroinflammation in Acute Brain Injury

急性脑损伤中的细胞神经炎症

• 批准号: MR/X021882/1
• 负责人: Adel Helmy
• 金额: $ 44.36万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX021882%2F1
• 关键词: Cellular; Neuroinflammation; Acute; Brain; Injury

Conditions that cause acute brain injury, such as trauma and brain haemorrhage are common causes of death and disability. Previous research has shown that much of the brain damage caused by these conditions occurs in the hours and days after the acute insult. This secondary damage is caused by inflammation that is triggered off by the primary insult. It is our belief that by understanding how this secondary inflammation occurs we will be able to identify targets for drug development. Drugs that control this secondary inflammation can potentially limit the brain damage resulting from these conditions. To date almost all brain injury research involving live tissue has focused on animal models, and unfortunately, little of what was learnt has been found to be directly relevant in humans; to date no effective treatments have emerged from these efforts. The need for research based on live human brain has long been recognised but until recently accessing such tissue was nearly impossible. In our hospital we have overcome this problem by establishing an ethically approved procedure to capture the tiny fragments of brain tissue that in the past where inevitably sacrificed and discarded during brain surgery. In acute brain injury severely affected patients have been shown to benefit from invasive monitoring using a small probe inserted into the brain itself. The insertion, and removal, of this probe involves the unavoidable loss of tiny fragments of brain. We are now able to capture this tissue for scientific research rather than it being thrown away. In this research, we will combine the analysis of this live human brain tissue with the results from the standard monitoring that we use in patients with significant brain injury. This technique, which we have pioneered, measures specialised signalling molecules called cytokines. These are proteins that immune cells use to communicate with each other. The levels of cytokines in the brain reflect the activity of the various parts of the immune system. The brain tissue we will collect will be processed into individual cells and characterised using a technique called single cell mRNA sequencing. This analysis will thus allow us to establish which cells are present after injury and which cells are making or responding to the cytokines we measure. Because we will take two brain tissue samples from each subject we will be able to measure how the cells change over time during brain injury. In total we will collect samples from 20 patients with severe brain injury: we will also collect samples from patients undergoing planned neurosurgery, either without any brain injury (10 patients) or more than 3 months after a brain injury (10 patients). We believe that the increased understanding of human brain inflammation that our work will provide will transform the prospects for developing safe and effective immune based treatments.

造成急性脑损伤的情况，如创伤和脑出血，是死亡和残疾的常见原因。先前的研究表明，这些情况引起的大部分脑损伤发生在急性损伤后的几小时和几天内。这种继发性损伤是由原发性损伤引发的炎症引起的。我们相信，通过了解这种继发性炎症是如何发生的，我们将能够确定药物开发的靶点。控制这种继发性炎症的药物可以潜在地限制由这些条件引起的脑损伤。到目前为止，几乎所有涉及活组织的脑损伤研究都集中在动物模型上，不幸的是，很少有研究发现与人类直接相关;迄今为止，这些努力还没有产生有效的治疗方法。人们早就认识到需要基于活的人类大脑进行研究，但直到最近，接近这种组织几乎是不可能的。在我们的医院，我们已经克服了这个问题，建立了一个道德上批准的程序，以捕捉微小的脑组织碎片，在过去的脑手术中不可避免地牺牲和丢弃。在急性脑损伤中，严重影响的患者已被证明受益于使用插入大脑本身的小探针进行侵入性监测。探针的插入和取出不可避免地会丢失大脑的微小碎片。我们现在能够捕获这些组织用于科学研究，而不是将其丢弃。在这项研究中，我们将联合收割机结合对活体人脑组织的分析和我们在严重脑损伤患者中使用的标准监测结果。这项技术是我们开创的，它测量称为细胞因子的专门信号分子。这些是免疫细胞用来相互交流的蛋白质。大脑中细胞因子的水平反映了免疫系统各个部分的活动。我们将收集的脑组织将被加工成单个细胞，并使用一种称为单细胞mRNA测序的技术进行表征。因此，这种分析将使我们能够确定哪些细胞在损伤后存在，哪些细胞正在产生或响应我们测量的细胞因子。因为我们将从每个受试者身上取两个脑组织样本，我们将能够测量脑损伤期间细胞如何随时间变化。我们总共将从20例重度脑损伤患者中收集样本：我们还将从接受计划神经外科手术的患者中收集样本，无论是无任何脑损伤（10例患者）还是脑损伤后超过3个月（10例患者）。我们相信，我们的工作将提供对人类大脑炎症的更多了解，这将改变开发安全有效的免疫治疗的前景。