Delayed neuronal death after peripheral nerve and spinal cord injury

周围神经和脊髓损伤后迟发性神经元死亡

• 批准号: nhmrc : 400918
• 负责人: E/Pr Elspeth Mclachlan
• 金额: $ 30.49万
• 依托单位: The University of New South Wales
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/delayed-neuronal-death-cord-injury/76176
• 关键词: Delayed; neuronal; death; after; peripheral

After injury to the nervous system, even under optimal conditions for regeneration of broken nerve processes (axons), there is little chance of normal function being restored because few regrowing axons will find appropriate cells to connect with. The time taken for many regrowing axons to reach their targets can be so long that both the axons and their targets lose the ability to recognize each other. Equally importantly, some damaged nerve cells die over the months that follow an injury. This slow loss of nerve cells can lead to progressive and ongoing deterioration. Given recent advances in our understanding of how to improve axon regeneration, the degree of functional recovery could be disappointing unless we know more about how to prevent these neurones from dying. This project will use rats as experimental animals to try to understand which types of nerve cells are likely to die or survive after injury to peripheral nerve trunks or to the spinal cord. We will investigate two regions of the nervous system that are commonly involved in injuries in people. After injuries to limb nerves, people lose sensation and movement and can unpredictably develop chronic conditions such as neuropathic pain (unrelated to the damage and often occurring spontaneously) as well as poor blood flow and wound healing in the hands-feet. After most injuries to the spinal cord, the lower part of the cord beyond the injury (in particular the lumbosacral cord controlling hindlimb movement and sensation and the function of bladder, bowel and sexual organs) is often disconnected from the brain leading to paralysis and disrupted control of pelvic organ function. We will identify and study specific populations of nerve cells with sensory (mainly pain-sensing) functions and four identified groups of nerve cells in the lumbosacral cord that project to the brain. Once we know which nerve cells do not survive, we will search for the likely causes of their death and ways to prevent it.

在神经系统损伤后，即使在断裂的神经过程（轴突）再生的最佳条件下，恢复正常功能的机会也很小，因为很少有再生的轴突会找到合适的细胞连接。许多再生的轴突到达目标所需的时间可能很长，以至于轴突和它们的目标都失去了识别彼此的能力。同样重要的是，一些受损的神经细胞在受伤后的几个月内死亡。这种神经细胞的缓慢损失可能导致进行性和持续性的恶化。鉴于我们对如何改善轴突再生的理解最近取得了进展，除非我们知道更多关于如何防止这些神经元死亡的知识，否则功能恢复的程度可能会令人失望。该项目将使用大鼠作为实验动物，试图了解哪些类型的神经细胞在外周神经干或脊髓损伤后可能死亡或存活。我们将研究神经系统的两个区域，这两个区域通常与人的损伤有关。在肢体神经损伤后，人们会失去感觉和运动，并可能不可预测地发展成慢性疾病，如神经性疼痛（与损伤无关，通常自发发生）以及手足血液流动不良和伤口愈合。在大多数脊髓损伤后，损伤之外的脊髓下部（特别是控制后肢运动和感觉以及膀胱、肠和性器官功能的腰骶脊髓）通常与大脑断开，导致瘫痪和对骨盆器官功能的控制中断。我们将鉴定和研究具有感觉（主要是疼痛感觉）功能的特定神经细胞群，以及腰骶髓中投射到大脑的四组已鉴定的神经细胞。一旦我们知道哪些神经细胞不能存活，我们将寻找它们死亡的可能原因和预防方法。