Skull-meninges-brain connectivity and extra-axial brain tumours

Abstract

The cortex of the brain is covered by three meningeal layers: the dura, the arachnoid, and the pia mater. Substantial discoveries have been made demonstrating the structural and functional relationships between these layers, and with other neighbouring structures such as the skull. Importantly, improved understanding of the meningeal lymphatic network places the meninges at the nexus of a cross talk between the brain, peripheral immune system, and the skull bone marrow. The meningeal lymphatic network has been shown to regulate immune responses in models of health and disease states, such as intra-axial brain tumours, affecting a tumour's behaviour. Unsurprisingly, a diverse array of resident and circulating immune cells such as macrophages, T-cells and B-cells can be found in the meninges, with specialized organizations or hubs surrounding the dural venous sinuses and cranial nerves. Meningioma and vestibular schwannoma are the most common extra-axial brain tumours, with varying clinical courses related to their immune microenvironments. These tumours commonly occur in proximity to the immune hubs of the meninges. This could point towards a possible bidirectional interaction, not only implicated in regulating tumour immune cell infiltration, but also meningeal inflammation and symptoms such as headaches and anxiety. This review will summarize the meningeal structure and function and highlight how these may be linked to patients with meningioma or vestibular schwannoma.

Keywords: immune; lymphatics; meninges; meningioma; vestibular schwannoma.

Graphical Abstract

Figure 1

A schematic description of the meninges and their structures. Connecting the skull bone marrow and the dura are skull–meningeal channels, which allow bidirectional exchange of immune cells, antigens and signalling molecules. The dural venous sinuses drain the brain parenchyma venous return via bridging veins. At the point of entry of these veins into the dura are stomas which have been called the arachnoid cuff exits (ACE), which allow bidirectional exchange of CSF and its components such as immune cells and antigens, across an otherwise impermeable membrane. Surrounding dural venous sinuses are a variety of immune cells such as macrophages, T-cells, B-cells, and plasma cells. Running alongside the dural venous sinuses are the lymphatic vessels, which are thought to contribute to draining CSF, into the cervical lymph nodes.

Figure 2

The meningeal lymphatic network. Lymphatic vessels run in the dura alongside the superior sagittal sinus, transverse sinus, confluence of sinuses, and sigmoid sinus, and alongside cranial nerves before draining into the cervical lymph nodes.