The Clearance Mechanisms in Central Nervous System: Roles of Vascular Basement Membrane Heparan Sulphate Proteoglycan Perlecan and Endothelial Growth Factor Angiopoietin-2

The central nervous system (CNS) is metabolically active but lacks a lymphatic drainage that strongly enhances tissue clearance. Recently proposed alternative mechanisms to maintain the CNS homeostasis include fluid flow in the perivascular spaces (PVS) along blood vessels (BVs), cranial nerves, and through lymphatic vessels (LVs) in meninges and nasal submucosa. The PVS and BVs are surrounded by a basement membrane (BM) composed of large, glycosylated proteins. Moreover, the development and function of both LVs and BVs are regulated by various growth factors. Currently, the specific roles of BM constituents in the clearance function is poorly known and not all potent signalling pathways for meningeal vascular development are characterized. This thesis investigates the importance of the major BM heparan sulphate proteoglycan perlecan and the pro-lymph/angiogenic angiopoietin-2 (Angpt2) growth factor in maintaining CNS fluid homeostasis.