Pan Jingxi, Fu Yinqi, Yang Peng, Li Wenfu, Luo Zhifeng, Zhang An, Du Jiashu, Mei Fen, Liu Fan, Qi Songtao, Bao Yun
The First Clinical College, Southern Medical University, Guangzhou, Guangdong, China.
Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Cell Mol Neurobiol. 2025 Aug 19;45(1):80. doi: 10.1007/s10571-025-01598-2.
The meninges serve as critical barriers that maintain immune homeostasis in the central nervous system (CNS) and play vital roles in immune surveillance and defense. Traditionally, the brain has been regarded as an "immune-privileged" organ owing to the absence of conventional lymphatic vessels. However, the rediscovery of meningeal lymphatic vessels (MLVs) has revealed a mechanism for the directional transport of cerebrospinal fluid (CSF) to the deep cervical lymph nodes (dCLNs), demonstrating that the brain possesses a distinct fluid communication pathway with the peripheral system that is independent of blood circulation. Additionally, the identification of the glymphatic system has revealed a perivascular mechanism for solute exchange between the CSF and brain parenchyma, primarily mediated by the astrocytic water channel protein aquaporin-4 (AQP4). These discoveries have significantly expanded our understanding of brain fluid dynamics and CNS homeostasis. This review provides a comprehensive overview of the structure, regulation, and function of MLVs and the glymphatic system, which together constitute lymphatic system of the brain. We also discuss recent evidence, particularly conflicting perspectives, on the role of meningeal immunity in various central nervous system (CNS) disorders, such as multiple sclerosis, Parkinson's disease, and epilepsy. Furthermore, we explore the therapeutic potential of targeting the brain lymphatic system to treat these conditions. Given their critical roles in CNS homeostasis, MLVs and the glymphatic system have emerged as promising therapeutic targets, potentially offering novel treatment strategies for currently incurable neurological diseases.
脑膜是维持中枢神经系统（CNS）免疫稳态的关键屏障，在免疫监视和防御中发挥着至关重要的作用。传统上，由于缺乏传统淋巴管，大脑一直被视为“免疫特权”器官。然而，脑膜淋巴管（MLV）的重新发现揭示了脑脊液（CSF）向深部颈淋巴结（dCLN）定向运输的机制，表明大脑拥有一条与外周系统独立于血液循环的独特液体通讯途径。此外，类淋巴系统的发现揭示了一种CSF与脑实质之间溶质交换的血管周围机制，主要由星形胶质细胞水通道蛋白水通道蛋白4（AQP4）介导。这些发现显著扩展了我们对脑液动力学和CNS稳态的理解。本综述全面概述了MLV和类淋巴系统的结构、调节和功能，它们共同构成了脑淋巴系统。我们还讨论了关于脑膜免疫在各种中枢神经系统（CNS）疾病，如多发性硬化症、帕金森病和癫痫中作用的最新证据，特别是相互矛盾的观点。此外，我们探讨了靶向脑淋巴系统治疗这些疾病的治疗潜力。鉴于它们在CNS稳态中的关键作用，MLV和类淋巴系统已成为有前景的治疗靶点，可能为目前无法治愈的神经疾病提供新的治疗策略。
