Identification of lymphatic endothelium in cranial arachnoid granulation-like dural gap

The dynamics of cerebrospinal fluid (CSF) are essential for maintaining homeostasis in the central nervous system. Despite insufficiently detailed descriptions of their structural and molecular properties for a century, cranial arachnoid granulations (CAGs) on meninges have been thought to participate in draining CSF from the subarachnoid space into the dural sinuses. However, recent studies have demonstrated the existence of other types of CSF drainage systems, such as lymphatic vessels adjacent to dural sinus and paravascular space in the brain so-called glymphatic system. Therefore, the role of CAGs in CSF drainage has become dubious. To better understand CAG function, we analyzed the ultrastructure and molecular identity of CAG-like structure on meninges adjacent to the superior sagittal sinus of pigs. Transmission electron microscopy analysis revealed that this structure has a reticular conglomerate consisting of endothelial cells that resembles lymphatic linings. Furthermore, immunohistochemistry and immunoelectron microscopy showed that they express molecules specific to lymphatic endothelial cell. We coined a name ‘CAG-like dural gap (CAG-LDG)’ to this structure and discussed the physiological relevance in terms of CSF drainage.