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

创伤性脑损伤(TBI)通常被认为是一种急性自限性问题。然而，在许多患者中，它可能导致慢性残疾。在相当大的少数群体中，这种残疾可能是渐进性的。事实上，我们现在知道，无论是单次严重的脑外伤，还是反复的轻度脑损伤，都会显著增加晚期痴呆的风险。据认为，脑外伤的这些晚期效应的很大一部分可能是由脑部炎症驱动的。事实上，我们很早就知道，患有严重脑外伤的患者脑部有严重的急性炎症。然而，越来越多的证据表明，这一过程在较轻微的脑损伤中也可能是重要的，并可能成为一个慢性过程。有趣的是，有来自脑外伤动物模型的建议，这种慢性炎症可能是因为身体对大脑产生了免疫反应，但目前尚不清楚这一过程对患者是有利还是有害。我们计划通过研究175名具有不同严重程度的脑外伤患者来研究这一问题。我们将观察血液和脑液中炎症细胞和分子的水平，并将其与一种名为正电子发射断层扫描(PET)的技术进行比较，正电子发射断层扫描使用小剂量的放射性示踪剂来成像大脑炎症，并与系列磁共振成像来绘制这种炎症的影响图。这些临床研究将以一系列动物研究为基础，这些研究将获得有关脑外伤后发生的脑部炎症类型的更详细信息，了解是什么驱动它产生伤害或好处，并调查新药在改善这一过程中的效果。我们相信，我们的研究可能使我们能够识别患有慢性炎症的患者，区分那些受到伤害的患者和那些从这一过程中受益的患者，并提供可能用于控制这一过程的特定患者亚群的药物。这意味着我们可能能够识别出作用更精确的药物，并将它们与特定患者的需求相匹配。这将代表着在目前的背景下取得了实质性的进展，在目前的背景下，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，并面临这样的风险，即许多患者可能没有从药物中获得任何好处，但仍然面临因其副作用而受到伤害的风险。

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.