Delayed neuronal death after peripheral nerve and spinal cord injury

神经系统损伤后，即使在受损神经突（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能找到合适的细胞连接。许多再生的轴突到达它们的目标所花费的时间很长，以至于轴突和它们的目标都失去了相互识别的能力。同样重要的是，一些受损的神经细胞会在受伤后的几个月内死亡。这种神经细胞的缓慢损失会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的进展，除非我们对如何防止这些神经元死亡有更多的了解，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，试图了解哪种类型的神经细胞在周围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体受伤有关。肢体神经受伤后，人们会失去感觉和运动能力，并可能出现不可预测的慢性疾病，如神经性疼痛（与损伤无关，通常是自发发生的），以及手脚血液流动不良和伤口愈合。在大多数脊髓损伤后，伤处以外的脊髓下部（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）往往与大脑断开，导致瘫痪和骨盆器官功能的控制中断。我们将识别和研究具有感觉（主要是痛觉）功能的特定神经细胞群，以及腰骶索中投射到大脑的四组已识别的神经细胞。一旦我们知道哪些神经细胞不能存活，我们就会寻找可能导致它们死亡的原因和预防方法。

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.