Promoting self-repair after Spinal Cord Injury

促进脊髓损伤后的自我修复

• 批准号: MR/X021947/1
• 负责人: Karel Dorey
• 金额: $ 100.27万
• 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: 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=MR%2FX021947%2F1
• 关键词: Promoting; self; repair; after; Spinal

Mammals, including humans, have a poor ability to repair their spinal cord upon injury. About 27 million people worldwide suffer long-term disability following spinal cord injury (SCI). Depending on the severity of the injury it can cause irreversible damage, which can lead to the loss of motor and sensory function below the site of the damage. This has far reaching consequences for the life of patients affected by SCI as they face lifelong confinement in a wheelchair, dependency on medical care and the risk of premature death. Therefore, there is a high requirement for improving regenerative capabilities of the spinal cord after injury.However, some vertebrates, such as zebrafish, the newt Axolotl and the tadpoles of the amphibian Xenopus can regenerate their spinal cord. Animal models are essential for biomedical research and Xenopus has unique advantages. It is easy to obtain large number of eggs, which develop externally and are accessible at all stages of development. The genome of Xenopus tropicalis has been sequenced and shows striking similarities with the human genome, meaning that findings from Xenopus provide insight into many human conditions and diseases. Finally, Xenopus sits at an interesting juncture in term of regeneration. During its tadpole stages, Xenopus can regenerate most tissues including its spinal cord however this ability is lost after metamorphosis, allowing comparative studies within one species.We and others have developed tools and resources to make Xenopus a relevant model to study spinal cord development, function and regeneration. The spinal cord is a complex tissue comprising undifferentiated cells (called progenitors) and many different types of differentiated neurons that need to work together. We have shown that the Xenopus spinal cord is very similar to that of mammals, making it a relevant model to study its regeneration. A hallmark of successful repair of regeneration of neural tissue is the ability of progenitors to generate new neurons, a process known as neurogenesis.The goal of this project is to uncover the mechanisms that promote neurogenesis during spinal cord regeneration in Xenopus. We will then use this knowledge to stimulate neurogenesis in a mammalian model of spinal cord injury. This research will provide an important platform to develop innovative strategies to improve the outcome of patients suffering from spinal cord injury.

包括人类在内的哺乳动物在受伤后修复脊髓的能力很差。全世界约有2700万人在脊髓损伤（SCI）后遭受长期残疾。根据损伤的严重程度，它可能会导致不可逆的损伤，这可能会导致损伤部位以下的运动和感觉功能丧失。这对受SCI影响的患者的生活产生了深远的影响，因为他们面临终身坐在轮椅上，依赖医疗护理和过早死亡的风险。因此，对脊髓损伤后再生能力的提高有很高的要求，而有些脊椎动物，如斑马鱼、蝾螈、两栖动物爪蟾的蝌蚪等都能再生脊髓。动物模型是生物医学研究的基础，而爪蟾具有独特的优势。很容易获得大量的卵子，这些卵子在外部发育，并且在发育的各个阶段都可以获得。非洲爪蟾的基因组已经被测序，并显示出与人类基因组惊人的相似性，这意味着非洲爪蟾的发现提供了对许多人类状况和疾病的见解。最后，爪蟾在再生方面处于一个有趣的时刻。在蝌蚪阶段，爪蟾可以再生包括脊髓在内的大部分组织，但这种能力在变态后丧失，允许在一个物种内进行比较研究。我们和其他人开发了工具和资源，使爪蟾成为研究脊髓发育，功能和再生的相关模型。脊髓是一个复杂的组织，包括未分化的细胞（称为祖细胞）和许多不同类型的分化的神经元，需要一起工作。我们已经表明，非洲爪蟾脊髓是非常相似的哺乳动物，使其成为一个相关的模型，以研究其再生。神经组织再生成功修复的一个标志是祖细胞产生新神经元的能力，这一过程被称为神经发生。本项目的目标是揭示非洲爪蟾脊髓再生过程中促进神经发生的机制。然后，我们将利用这些知识来刺激脊髓损伤的哺乳动物模型中的神经发生。这项研究将提供一个重要的平台，以开发创新的策略，以改善脊髓损伤患者的预后。