圣路易斯的华盛顿大学Jonathan Kipnis研究团队的一项最新研究报道了肥大细胞调节脑-硬脑膜界面和脑脊液动力学。相关论文于2025年7月24日发表在《细胞》杂志上。

研究组发现硬脑膜肥大细胞调节脑脊液在ACE点的动态。脱颗粒后，肥大细胞释放组胺，诱导桥静脉的血管扩张，减少对脑脊液引流至关重要的血管周围空间。在细菌性脑膜炎期间，病原体利用ACE点进入大脑。

然而，肥大细胞激活可重定向脑脊液流动，招募中性粒细胞，并限制细菌入侵。缺乏硬脑膜肥大细胞的小鼠表现出免疫反应受损和更高的脑细菌负荷。这些发现表明硬脑膜肥大细胞在调节脑脊液流和脑膜免疫中起着核心作用。靶向肥大细胞或其介质可能增强中枢神经系统的清除和防御机制，为脑感染提供了潜在的治疗途径。

据悉，脑脊液（CSF）流动对脑内稳态至关重要，其破坏与神经退行性和神经炎性疾病有关。蛛网膜袖口（ACE）点是桥静脉周围蛛网膜的解剖不连续点，是脑脊膜-硬脑膜交换的关键部位。

附：英文原文

Title: Mast cells regulate the brain-dura interface and CSF dynamics

Author: Tornike Mamuladze, Tiago H. Zaninelli, Leon C.D. Smyth, Yue Wu, Daviti Abramishvili, Ruben Silva, Brian Imbiakha, Daan Verhaege, Siling Du, Zachary Papadopoulos, Xingxing Gu, David Lee, Steffen Storck, Richard J. Perrin, Igor Smirnov, Xinzhong Dong, Song Hu, Michael S. Diamond, Felipe A. Pinho-Ribeiro, Jonathan Kipnis

Issue&Volume: 2025-07-24

Abstract: Cerebrospinal fluid (CSF) flow is essential for brain homeostasis, and its disruption is implicated in neurodegenerative and neuroinflammatory diseases. Arachnoid cuff exit (ACE) points, anatomical discontinuities in the arachnoid mater around bridging veins, serve as key sites of CSF-dura exchange. Here, we show that dural mast cells regulate CSF dynamics at ACE points. Upon degranulation, mast cells release histamine, inducing vasodilation of bridging veins and reducing perivascular spaces critical for CSF drainage. During bacterial meningitis, pathogens exploit ACE points to access the brain. However, mast cell activation redirects CSF flow, recruits neutrophils, and limits bacterial invasion. Mice lacking dural mast cells exhibit impaired immune responses and higher brain bacterial loads. These findings reveal dural mast cells as central players in modulating CSF flow and meningeal immunity. Targeting mast cells or their mediators may enhance CNS clearance and defense mechanisms, offering a potential therapeutic avenue for brain infections.

DOI: 10.1016/j.cell.2025.06.046

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00748-2