Functional implications of focal white matter lesions on neuronal circuits

多发性硬化症（MS）和其他神经退行性疾病，如痴呆、阿尔茨海默氏症和帕金森病，对人们的生活和社会产生了很大的影响。目前还没有完全有效的治疗方法来阻止这些疾病的发展。人类的大脑被平分为两半：灰质和白质。大多数关于神经退行性疾病的研究都集中在含有神经元的大脑灰质上，但忽视了白质的作用。新的研究表明，大脑白质内的损伤发生在神经退行性疾病中。这些损伤的数量与思维和运动问题有关。重要的是，这些病变可以在人们出现任何症状之前出现，表明这些病变可能在疾病进展中起作用。多发性硬化症的特征是大脑中的白质病变，从多发性硬化症的研究中我们知道白质病变是可以修复的，这使得症状完全恢复。这是因为我们的大脑中有专门的干细胞可以修复白质损伤。尽管在多发性硬化症中白质损伤可以修复，但这种再生过程最终会失败，随着年龄的增长，这种情况会更多。白质损伤修复失败可导致神经元丢失（神经退行性变）、持续的脑部炎症和残疾。大脑炎症是一种低水平的持续过程，在神经退行性疾病和多发性硬化症中都很常见。我们的早期动物研究结果表明，修复白质病变可以减少大脑灰质和白质的炎症。看来，未能正确修复白质损伤可能导致持续的脑部炎症。我们的数据显示，大脑中的炎症和神经元的变化是触发白质修复的必要条件。这表明，为了开发有效的治疗方法，我们需要了解炎症、神经元和白质病变是如何相互作用的，因为只针对灰质或免疫系统等部分，可能不足以防止进一步的损害。我们的研究旨在通过研究白质病变如何影响脑功能、灰质炎症以及白质病变的修复如何被调节来填补这一知识空白。我们希望更多地了解神经退行性疾病，以及修复白质病变是否可以减少大脑炎症，这可能会导致神经元的损失。这项研究可能会导致新的治疗方法的发展，重点是修复大脑的白质，以保持大脑的功能。最终，我们的目标是减轻这些疾病对个人、家庭和整个社会的负担。

Multiple sclerosis (MS) and other neurodegenerative disorders like dementia, Alzheimer's, and Parkinson's disease have a large impact on people's lives and society. There are no fully effective treatments available to stop these diseases from progressing.The human brain is divided into two equal halves: grey and white matter. Most of the research on neurodegenerative disorders has focused on the grey matter of the brain, which contains the neurons, but has overlooked the role of the white matter. New research is showing that lesions within the brain's white matter occur in neurodegenerative disorders. The number of these lesions is linked to problems with thinking and movement. Importantly, these lesions can appear before people experience any symptoms, indicating that these lesions may have a role to play in the disease progression.MS is characterised by white matter lesions in the brain, and from MS research we know that white matter lesions can be repaired, which allows for full symptomatic recovery. This is because in our brain we have specialised stem cells that can repair white matter lesions. Although white matter lesions can be repaired in MS, this regeneration process eventually fails, more so as we age. The failure of repairing white matter lesions can lead the loss of neurons (neurodegeneration), ongoing brain inflammation, and disability.Inflammation in the brain, which is a low-level and ongoing process, is common in both neurodegenerative conditions and MS. Our early results from animal studies suggest that repairing white matter lesions reduces inflammation in both the grey and white matter of the brain. It seems that the failure to repair white matter lesions properly may be causing the ongoing brain inflammation. Our data show that inflammation in the brain and changes in neurons are necessary to trigger white matter repair. This suggests that we need to understand how inflammation, neurons, and white matter lesions interact in order to develop effective treatments, as targeting only one part, like the grey matter or the immune system, may not be enough to prevent further damage.Our research aims to fill this knowledge gap by studying how white matter lesions affect brain function, grey matter inflammation and how repair of white matter lesions is regulated. We hope to learn more about neurodegenerative diseases and whether repairing white matter lesions can reduce brain inflammation, which may be causing the loss of neurons. This research could lead to the development of new treatments that focus on repairing the brain's white matter to preserve brain function. Ultimately, our goal is to reduce the burden of these diseases on individuals, families, and society as a whole.