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The central nervous system is separated by the dura, arachnoid and pia mater, which has the effect of supporting and nourishing thebrain.
The dura mater is synthesized by two layers, blood vessels and nerves travel between the two layers, and the zou fold formed by the pia mater protrudes into the ventricle to form a choroid plexus and secrete cerebrospinal fluid
.
Cardiovascular pulsations drive cerebrospinal fluid along the surrounding space into the deep brain and internechymal exchange
via glial aquaporin 4.
Cerebrospinal fluid is excreted by a network of lymphatic vessels in the meninges, and this excretion is impaired to accelerate the aggregation of proteins, causing cognitive dysfunction
.
There is a large gap between the arachnoid membrane and the pia mater, called the subarachnoid space
.
On January 6, 2023, the research team of Maiken Nedergaard at the University of Rochester Medical Center redefined the meningeal system of the brain, discovering the presence of a class of lymphoid membranes present in the subarachnoid space, which divided the chamber into two parts to become the fourth membrane structure
of the brain.
Figure 1: Subarachnoid lymphoid membrane (SLYM) structure diagram
Prospero-associated homologous box protein 1 (PROX1) is a highly conserved transcriptional regulator of lymphatic fate that can be used to label lymphangioendothelial cell markers.
The researchers observed the Prox1-EGFP tool mouse somatosensory cortex region through two-photon microscopy and found that beneath the collagen bundle parallel to the dura mater, there was a continuous, flat layer of Prox1-EGFP+ monolayer of cells mixed with loose collagen fibers called the subarachnoid lymphoid membrane (SLYM).
Further analysis found that SLYM thickness was 14.
2 um, covering subarachnoid blood vessels, while dura mater had an average thickness of 21.
8 um, surrounded by collagen fibers, and there were obvious structural differences
between the two.
Whole-brain structural analysis revealed that SLYM was in direct contact with sinus endothelial cells, which was a villous structure
in the subarachnoid space on the wall of the venous sinus.
SLYM is also found in human cortical tissues throughout the subarachnoid space
.
Figure 2: SLYM is in close contact with sinus endothelial cells
Prox1-EGFP mouse red fluorophore-bound 1 micron microspheres were injected into the subarachnoid subdural superficial compartment, while 1 micron blue light fluorescent microspheres were injected into the deep subarachnoid compartment, and these fluorophores were found to not penetrate
each other.
In addition, permeability experiments have found that molecules of 3 kDa and above are not allowed to pass through
.
This suggests that SLYM is a barrier that subdivides the subarachnoid space into two chambers, the upper superficial layer and the lower deep layer
.
Prox1-EGFP+ SLYM cells also express another lymphatic marker, PDPN, and cellular tretinoin-binding protein 2 (CRABP2), indicating that it is a lympho-dependent structure
.
Further fluorescence experiments showed that SLYM did not express CLDN-11, the main component of the tight junction of the arachnoid barrier cell layer, nor did it express lymphangioendothelial receptor 1, a marker of arachnoid trabeculae
.
These results suggest that SLYM is not part of the arachnoid membrane, but the fourth meningeal layer
that surrounds the brain.
Figure 3: SLYM hosts a variety of immune cells
The researchers found the presence of a large number of white blood cells in SLYM through two-photon microscopy, and the leukocyte aggregation in SLYM was significantly increased after intraperitoneal injection of lipopolysaccharides, and this abnormal aggregation was also found inaging mice.
In addition, macrophages and dendritic cells are also present in SLYM, suggesting that SLYM can function as a key microenvironment
for immune cells.
This paper found that in both mouse and human brains there is a fourth layer of meningea-SLYM, which separates the subarachnoid space, which wraps blood vessels and is closely connected to the venous sinus endothelium, allowing cerebrospinal fluid and venous blood to exchange
substances.
At the same time, SLYM hosts a variety of immune cells, providing a new perspective
for the study of brain immune barrier and fluid transport function.
【References】
Møllgård et al.
, Science 379, 84–88 (2023)，A mesothelium divides the subarachnoid space into functional compartments
The images in the article are from references
