Papadopoulos Zachary, Smyth Leon C D, Smirnov Igor, Gibson Daniel A, Herz Jasmin, Kipnis Jonathan
Brain Immunology and Glia (BIG) Center, Washington University in St. Louis , St. Louis, MO, USA.
Department of Pathology and Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
J Exp Med. 2025 Feb 3;222(2). doi: 10.1084/jem.20241752. Epub 2025 Jan 8.
Dysfunctional lymphatic drainage from the central nervous system (CNS) has been linked to neuroinflammatory and neurodegenerative disorders, but our understanding of the lymphatic contribution to CNS fluid autoregulation remains limited. Here, we studied forces that drive the outflow of the cerebrospinal fluid (CSF) into the deep and superficial cervical lymph nodes (dcLN and scLN) and tested how the blockade of lymphatic networks affects CNS fluid homeostasis. Outflow to the dcLN occurred spontaneously in the absence of lymphatic pumping and was coupled to intracranial pressure (ICP), whereas scLN drainage was driven by pumping. Impaired dcLN drainage led to elevated CSF outflow resistance and delayed CSF-to-blood efflux despite the recruitment of the nasal-to-scLN pathway. Fluid regulation was better compensated after scLN obstruction. The dcLN pathway exhibited steady, consistent drainage across conditions, while the nasal-to-scLN pathway was dynamically activated to mitigate perturbances. These findings highlight the complex physiology of CSF homeostasis and lay the groundwork for future studies aimed at assessing and modulating CNS lymphatic function.
中枢神经系统（CNS）功能失调的淋巴引流与神经炎症和神经退行性疾病有关，但我们对淋巴系统在CNS液体自动调节中的作用的理解仍然有限。在这里，我们研究了驱动脑脊液（CSF）流入深部和浅表颈淋巴结（dcLN和scLN）的力量，并测试了淋巴网络的阻断如何影响CNS液体稳态。在没有淋巴泵浦的情况下，脑脊液自发地流入dcLN，且与颅内压（ICP）相关，而scLN的引流则由泵浦驱动。尽管募集了鼻至scLN途径，但dcLN引流受损导致脑脊液流出阻力升高和脑脊液至血液的外排延迟。scLN阻塞后，液体调节得到更好的补偿。dcLN途径在各种条件下均表现出稳定、一致的引流，而鼻至scLN途径则被动态激活以减轻干扰。这些发现突出了脑脊液稳态的复杂生理学，并为未来旨在评估和调节CNS淋巴功能的研究奠定了基础。
