The role of vascular immune cells in recovery after brain haemorrhage

血管免疫细胞在脑出血后恢复中的作用

• 批准号: 2897409
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2897409
• 关键词: role; vascular; immune; cells; recovery

Intracerebral haemorrhage (ICH) is a stroke subtype caused by spontaneous bleeding into brain tissue. ICH is responsible for over half of the 6.5 million stroke-related deaths annually worldwide and accounts for the majority of the disability burden of stroke, with 80% of ICH patients remaining dependent on others in the long-term1. Despite the considerable and ongoing burden of ICH, there remain few effective therapies to improve outcome and help the brain repair. After ICH there is activation of multiple repair mechanisms including those to stimulate the formation of new blood vessels, which help to restore blood flow and oxygen supply to the damaged brain tissue, and therefore aid in the functional recovery of the blood-brain barrier (BBB). However, despite activation of these regenerative mechanisms, the level of tissue repair is typically insufficient for full restoration of function. Thus, discovering new ways to modulate blood vessel formation and blood flow could be a promising therapeutic strategy after ICH. Perivascular macrophage cells are a small population of specialised macrophages localised around some blood vessels in the brain. Emerging evidence suggest that these perivascular cells may play a role in outcome after stroke2. Our preliminary work has also shown that perivascular macrophages accumulate around the haemorrhage and they might be important in long-term outcome and recovery. This PhD will therefore study the role of these perivascular macrophage cells after ICH and will test the hypothesis that they help to repair the brain vasculature and improve blood flow. To address this hypothesis, the student will use a well-established rodent model of haemorrhage coupled with magnetic resonance imaging (MRI), behavioural tests and ex vivo analysis including analysis of immune cells. This project provides a great opportunity to join a vibrant research group and the student will receive an interdisciplinary training in an exciting area of research which could improve our understanding of a devastating disease and lead to the development of a new treatment option.

脑出血（ICH）是由自发性出血进入脑组织引起的卒中亚型。在全球每年650万例卒中相关死亡中，ICH占一半以上，占卒中残疾负担的大部分，80%的ICH患者长期依赖他人1。尽管ICH的负担相当大且持续存在，但仍然很少有有效的治疗方法来改善结果并帮助大脑修复。脑出血后，多种修复机制被激活，包括刺激新血管形成的机制，这有助于恢复受损脑组织的血流和氧气供应，因此有助于血脑屏障（BBB）的功能恢复。然而，尽管激活了这些再生机制，但组织修复的水平通常不足以完全恢复功能。因此，发现调节血管形成和血流的新方法可能是ICH后有前途的治疗策略。血管周围巨噬细胞是一小群专门的巨噬细胞，位于大脑中的一些血管周围。新出现的证据表明，这些血管周围细胞可能在中风后的结果中发挥作用2。我们的初步工作还表明，血管周围巨噬细胞聚集在出血周围，它们可能对长期预后和恢复很重要。因此，本博士将研究这些血管周围巨噬细胞在ICH后的作用，并将测试它们有助于修复脑血管和改善血流的假设。为了解决这一假设，学生将使用一个完善的啮齿动物模型出血加上磁共振成像（MRI），行为测试和离体分析，包括免疫细胞的分析。该项目提供了一个很好的机会，加入一个充满活力的研究小组，学生将在一个令人兴奋的研究领域接受跨学科的培训，这可以提高我们对毁灭性疾病的理解，并导致新的治疗方案的发展。