Noé Francesco M, Marchi Nicola
Neuro-Lymphatic Group A.I. Virtanen Institute for Molecular Sciences University of Eastern Finland Kuopio Finland.
Biology of Neuro-Immune Interaction HiLife-Neuroscience Center Helsinki University Helsinki Finland.
Epilepsia Open. 2019 Feb 14;4(1):30-39. doi: 10.1002/epi4.12302. eCollection 2019 Mar.
The recent definition of a network of lymphatic vessels in the meninges surrounding the brain and the spinal cord has advanced our knowledge on the functional anatomy of fluid movement within the central nervous system (CNS). Meningeal lymphatic vessels along dural sinuses and main nerves contribute to cerebrospinal fluid (CSF) drainage, integrating the cerebrovascular and periventricular routes, and forming a circuit that we here define as the CNS-lymphatic unit. The latter unit is important for parenchymal waste clearance, brain homeostasis, and the regulation of immune or inflammatory processes within the brain. Disruption of fluid drain mechanisms may promote or sustain CNS disease, conceivably applicable to epilepsy where extracellular accumulation of macromolecules and metabolic by-products occur in the interstitial and perivascular spaces. Herein we address an emerging concept and propose a theoretical framework on: (a) how a defect of brain clearance of macromolecules could favor neuronal hyperexcitability and seizures, and (b) whether meningeal lymphatic vessel dysfunction contributes to the neuroimmune cross-talk in epileptic pathophysiology. We propose possible molecular interventions targeting meningeal lymphatic dysfunctions, a potential target for immune-mediated epilepsy.
最近对围绕大脑和脊髓的脑膜中淋巴管网络的定义，推进了我们对中枢神经系统（CNS）内液体流动功能解剖学的认识。沿硬脑膜窦和主要神经的脑膜淋巴管有助于脑脊液（CSF）引流，整合脑血管和脑室周围途径，并形成一个我们在此定义为CNS-淋巴单元的回路。后一个单元对于实质废物清除、脑内稳态以及脑内免疫或炎症过程的调节很重要。液体引流机制的破坏可能促进或维持中枢神经系统疾病，可以想象这适用于癫痫，其中大分子和代谢副产物在间质和血管周围空间发生细胞外积累。在此，我们探讨一个新出现的概念，并提出一个理论框架，内容包括：（a）大脑大分子清除缺陷如何促进神经元过度兴奋和癫痫发作，以及（b）脑膜淋巴管功能障碍是否在癫痫病理生理学中导致神经免疫相互作用。我们提出了针对脑膜淋巴功能障碍的可能分子干预措施，这是免疫介导性癫痫的一个潜在靶点。
