Highly dynamic dural sinuses support meningeal immunity

Summary

This Nature paper maps the anatomy and live behaviour of the dorsal dural venous sinuses in mice and compares features with human data to show that sinuses are not passive conduits but dynamically active interfaces that support meningeal immunity. Using light-sheet and two-photon intravital imaging, electron microscopy, micro-CT, human MRI/venography and single-cell RNA sequencing, the authors describe distinct upper (intra-skull) and lower (dural) superior sagittal sinuses, frequent anastomoses fed by diploic vessels and skull bone marrow channels, and highly dynamic sinus endothelial cell (SEC) membrane features — termed ruffles and openings — that enable immune cell trafficking and respond to neural and molecular signals.

Key Points

The superior sagittal sinus is anatomically two-tiered: an upper sinus embedded within skull bone and a lower sinus in the dura, connected by skull-penetrating anastomoses.
Sinus endothelial cells (SECs) display dynamic membrane ruffles and stable openings that permit leukocyte transit from the lumen into the perisinus space.
EM reveals SEC fenestrations and abundant caveolae, supporting transendothelial exchange distinct from parenchymal vessels.
Sinus calibre and SEC dynamics show vasomotion regulated by peripheral nerves and adrenergic/CGRP–RAMP signalling (RAMP1/2), and by Rho-associated kinase activity.
Infection (LCMV) and immune cell activity amplify SEC ruffling and recruitment of myeloid cells; prolonged RAMP2 inhibition blunts these dynamic responses.
Diploic veins and skull bone marrow form direct vascular inputs to sinuses, reinforcing the skull marrow–meningeal immune axis previously described.
scRNA-seq of sinus-associated endothelial cells highlights gene signatures (Plvap, Ramp2, Cldn5, Adm and others) consistent with specialised barrier and signalling functions.
Human venography/MRI and EM samples show conserved features, suggesting translational relevance to human meningeal immunity and disease processes (infection, migraine, intracranial hypertension).

Content summary

The authors combine multiple high-resolution imaging modalities with functional perturbations and transcriptomics to redefine dural sinuses as active neuroimmune interfaces. Anatomical reconstructions (CT, light-sheet, micro-CT) reveal an upper skull-resident sinus that drains rostrally and a lower dural sinus draining caudally; several large anastomoses and diploic vessels link bone marrow to the sinus network.

Two-photon intravital microscopy through thinned-skull windows shows continuous, spontaneous vasoconstriction and dilation of sinus walls, and identifies large, dynamic SEC membrane ruffles and discrete holes allowing cell passage. Electron microscopy documents endothelial fenestrations and caveolae that contrast with typical blood–brain barrier endothelium. Functional experiments demonstrate that peripheral nerve ablation, adrenergic antagonists, CGRP and RAMP modulation alter vasomotion and SEC dynamics. Infection models increase ruffling and myeloid cell interactions; blocking adhesion molecules or Rho kinase inhibits membrane dynamics. scRNA-seq profiles support specialised SEC identity and implicate RAMP signalling pathways in dynamic responses.

Context and relevance

This study builds on recent work showing the meninges and skull marrow are immunologically active and connected to the brain. By showing sinuses are structurally specialised, dynamically regulated and permissive for immune cell trafficking, the paper links vascular mechanics, neuropeptide signalling (CGRP, adrenergic), and skull marrow inputs to meningeal immune surveillance and responses. The findings are directly relevant to understanding meningitis, neuroinflammation, mechanisms of migraine (CGRP pathways), intracranial pressure disorders and routes of immune cell entry into the CNS. The cross-species evidence (mouse and human imaging/EM) strengthens translational potential.

Author style

Punchy: the authors reframe dural sinuses from inert drainage pipes to active, regulated immune hubs — a major shift. If you follow neuroimmunology, vascular biology or headache and intracranial pressure research, the mechanistic links they provide between endothelial dynamics, neural signalling and skull marrow inputs are important and worth the deep read.

Why should I read this?

Short answer: because it’s clever and changes how we think about the brain’s borders. The paper shows the sinuses move, open and close, and actually let immune cells through — under control from nerves and peptide signals. If you care about meningitis, migraine, or how immune cells access the CNS, this saves you the time of hunting through lots of scattered studies — the authors put the anatomy, live behaviour, molecular drivers and human relevance all in one place.

Source

Source: https://www.nature.com/articles/s41586-026-10165-8

Article metadata

Article Date: 18 February 2026
Article URL: https://www.nature.com/articles/s41586-026-10165-8
Article Title: Highly dynamic dural sinuses support meningeal immunity
Article Image: (not provided)