International Collaboration On Neuroinflammation in Traumatic Brain Injury (ICON-TBI)

创伤性脑损伤神经炎症国际合作 (ICON-TBI)

• 批准号: MR/R005036/1
• 负责人: David Menon
• 金额: $ 29.95万
• 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: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR005036%2F1
• 关键词: International; Collaboration; Neuroinflammation; Traumatic; Brain

Traumatic brain injury (TBI) is commonly thought of as an acute self-limited problem. However, in many patients, it can result in chronic disability. In a sizeable minority, such disability can be progressive. Indeed, we now know that either a single severe TBI, or repeated mild TBI, can substantially increase the risk of late dementia. It is believed that a substantial part of these late effects of TBI may be driven by brain inflammation. Indeed, we have known for a long time that patients who suffer a severe TBI have significant acute inflammation in the brain. However, there is increasing evidence that this process may also be important in milder forms of TBI, and that it can become a chronic process. Intriguingly, there are suggestions from animal models of TBI that some of this chronic inflammation may be because the body develops an immune response against the brain, but it is not clear whether this process is beneficial or harmful to patients. We plan to investigate this issue by studying 175 patients with a range of TBI severity. We will look at the levels of inflammatory cells and molecules in both blood and brain fluids, and compare this with a technique called positron emission tomography (PET), which uses small doses of radioactive tracers to image brain inflammation, and with serial magnetic resonance imaging to map the impact of such inflammation. These clinical studies will be underpinned by a portfolio of animal studies which will obtain more detailed information on the types of brain inflammation that occur after TBI, understand what drives it to produce harm or benefit, and investigate the effect of novel drugs in improving this process. We believe that our research may allow us to identify patients who develop chronic inflammation, differentiate those who experience harm from those who benefit from this process, and provide drugs that might be used to control this process in specific subgroups of patients. This holds the promise that we may be able to identify drugs that act more precisely, and match them to the needs of specific patients. This would represent a substantial advance on the present context, where we use drugs that have very wide actions on inflammation across an entire population of patients, and run the risk that many of these patients may not experience any benefit from the drug, but still be at risk of harm from its side effects.

外伤性脑损伤（TBI）通常被认为是一种急性自限性疾病。然而，在许多患者中，它可能导致慢性残疾。在相当大的少数人中，这种残疾可能是渐进的。事实上，我们现在知道，无论是一次严重的创伤性脑损伤，还是多次轻微的创伤性脑损伤，都会大大增加患晚期痴呆的风险。据信，创伤性脑损伤的这些晚期影响的很大一部分可能是由脑部炎症驱动的。事实上，我们早就知道，遭受严重创伤性脑损伤的患者在大脑中有明显的急性炎症。然而，越来越多的证据表明，这一过程可能在轻度创伤性脑损伤中也很重要，并且可能成为一种慢性过程。有趣的是，从创伤性脑损伤的动物模型中发现，一些慢性炎症可能是因为身体产生了针对大脑的免疫反应，但目前尚不清楚这个过程对患者是有益还是有害。我们计划通过研究175名不同程度的TBI患者来调查这个问题。我们将观察血液和脑液中炎症细胞和分子的水平，并将其与正电子发射断层扫描（PET）技术进行比较。正电子发射断层扫描使用小剂量的放射性示踪剂来成像脑部炎症，并使用连续磁共振成像来绘制这种炎症的影响。这些临床研究将以一系列动物研究为基础，这些动物研究将获得关于创伤性脑损伤后发生的脑部炎症类型的更详细信息，了解导致其产生危害或益处的原因，并研究新药在改善这一过程中的作用。我们相信，我们的研究可能使我们能够识别慢性炎症患者，区分那些从这一过程中受益的人，并提供可能用于控制特定亚组患者这一过程的药物。这给我们带来了希望，我们可能能够更精确地识别起作用的药物，并将它们与特定患者的需求相匹配。在目前的情况下，这将是一个实质性的进步，我们使用的药物对整个患者群体的炎症有非常广泛的作用，并且冒着许多患者可能不会从药物中获得任何好处，但仍然有可能因其副作用而受到伤害的风险。

项目成果

Dextran 500 Improves Recovery of Inflammatory Markers: An In Vitro Microdialysis Study.

右旋糖酐 500 改善炎症标志物的恢复：一项体外微透析研究。

• DOI: 10.17863/cam.41846
• 发表时间: 2020
• 作者: Giorgi-Coll S

A method to isolate and cryopreserve cerebrospinal fluid mononuclear cells from external ventricular drains to investigate immunological processes in acute brain injuries.

一种从脑室外引流中分离和冷冻保存脑脊液单核细胞的方法，以研究急性脑损伤的免疫过程。

• DOI: 10.1016/j.jim.2021.113163
• 发表时间: 2021
• 期刊: Journal of immunological methods
• 影响因子: 2.2
• 作者: Digby RJ

Contusion Progression Following Traumatic Brain Injury: A Review of Clinical and Radiological Predictors, and Influence on Outcome.

创伤性脑损伤后的挫伤进展：临床和放射学预测因素的回顾以及对结果的影响。

• DOI: 10.17863/cam.52402
• 发表时间: 2021
• 作者: Adatia K

Neuro-Inflammation Modulation and Post-Traumatic Brain Injury Lesions: From Bench to Bed-Side.

• DOI: 10.3390/ijms231911193
• 发表时间: 2022-09-23
• 期刊: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• 影响因子: 5.6
• 作者: Jacquens, Alice;Needham, Edward J.;Zanier, Elisa R.;Degos, Vincent;Gressens, Pierre;Menon, David
• 通讯作者: Menon, David

Cellular infiltration in traumatic brain injury.

• DOI: 10.1186/s12974-020-02005-x
• 发表时间: 2020-11-03
• 期刊: Journal of neuroinflammation
• 影响因子: 9.3
• 作者: Alam A;Thelin EP;Tajsic T;Khan DZ;Khellaf A;Patani R;Helmy A
• 通讯作者: Helmy A