PDF(Pubmed)
Abstract：
Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide, particularly among the elderly, yet our mechanistic understanding of what renders the post-traumatic brain vulnerable to poor outcomes, and susceptible to neurological disease, is incomplete. It is well established that dysregulated and sustained immune responses elicit negative consequences after TBI; however, our understanding of the neuroimmune interface that facilitates crosstalk between central and peripheral immune reservoirs is in its infancy. The meninges serve as the interface between the brain and the immune system, facilitating important bi-directional roles in both healthy and disease settings. It has been previously shown that disruption of this system exacerbates neuroinflammation in age-related neurodegenerative disorders such as Alzheimer\'s disease; however, we have an incomplete understanding of how the meningeal compartment influences immune responses after TBI. In this manuscript, we will offer a detailed overview of the holistic nature of neuroinflammatory responses in TBI, including hallmark features observed across clinical and animal models. We will highlight the structure and function of the meningeal lymphatic system, including its role in immuno-surveillance and immune responses within the meninges and the brain. We will provide a comprehensive update on our current knowledge of meningeal-derived responses across the spectrum of TBI, and identify new avenues for neuroimmune modulation within the neurotrauma field.
摘要：
创伤性脑损伤(TBI)是全球范围内致残和死亡的主要原因,尤其是老年人，然而，我们对创伤后大脑易受不良结果影响的机制理解，易患神经系统疾病，是不完整的。众所周知，失调和持续的免疫反应会在TBI后引发负面后果；然而，我们对促进中枢和外周免疫库之间串扰的神经免疫界面的理解尚处于起步阶段。脑膜是大脑和免疫系统之间的接口，在健康和疾病环境中促进重要的双向作用。以前已经表明，该系统的破坏会加剧与年龄相关的神经退行性疾病如阿尔茨海默病的神经炎症；然而，我们对脑膜室如何影响TBI后的免疫反应有不完全的了解。在这份手稿中,我们将提供TBI中神经炎症反应的整体性质的详细概述，包括在临床和动物模型中观察到的标志特征。我们将重点介绍脑膜淋巴系统的结构和功能，包括其在脑膜和大脑内的免疫监视和免疫反应中的作用。Wewillprovideacomprehensiveupdateonourcurrentknowledgeofmemingeal-derivedresponsesacrossthespectrumofTBI,并确定神经创伤领域内神经免疫调节的新途径。
