Mechanisms of interleukin-1 action in neuronal injury

IL-1在神经元损伤中的作用机制

• 批准号: G0801296/1
• 负责人: Nancy Rothwell
• 金额: $ 96.09万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0801296%2F1
• 关键词: Mechanisms; interleukin; action; neuronal; injury

The blood supply to the brain provides essential oxygen and nutrients to support brain function. During stroke, haemorrhage (bleeding), head injury and certain types of dementia, the blood supply to the brain may be partially reduced or blocked, with fatal consequences for the patient. Our work focuses on understanding what happens in the brain and the rest of the body when the blood supply is reduced, in order to develop safer and more effective treatments for stroke. We have discovered that, in animal brains, a molecule normally associated with inflammation and infection (called interleukin-1 or IL-1 for short) increases when the blood supply is blocked. IL-1 can then kill brain cells, most importantly the nerve cells (neurones), which are essential for the brain to work properly. Our work in animals has already led to the testing of a drug that blocks the effects of IL-1 in stroke patients. However, to develop successful treatments for stroke and other conditions, we need to better understand how IL-1 kills brain cells either directly or by releasing killer molecules from other brain cells. We will test our discoveries in relevant animal models of disease and are well placed to take these findings into patients. This work may lead to new ways of blocking IL-1 and possible new treatments for stroke and related diseases.

大脑的血液供应提供必要的氧气和营养物质来支持大脑功能。在中风、出血（出血）、头部受伤和某些类型的痴呆症期间，大脑的血液供应可能部分减少或阻塞，对患者造成致命后果。我们的工作重点是了解当血液供应减少时，大脑和身体其他部位会发生什么，以开发更安全，更有效的中风治疗方法。我们发现，在动物大脑中，当血液供应受阻时，通常与炎症和感染相关的分子（称为白细胞介素-1或简称IL-1）会增加。然后IL-1可以杀死脑细胞，最重要的是神经细胞（神经元），这是大脑正常工作所必需的。我们在动物身上的工作已经导致了一种药物的测试，这种药物可以阻断IL-1在中风患者中的作用。然而，为了开发成功的中风和其他疾病的治疗方法，我们需要更好地了解IL-1如何直接杀死脑细胞或通过释放其他脑细胞的杀伤分子来杀死脑细胞。我们将在相关的疾病动物模型中测试我们的发现，并将这些发现用于患者。这项工作可能会导致阻断IL-1的新方法，并可能为中风和相关疾病提供新的治疗方法。