Cerebral Vessels: An Overview of Anatomy, Physiology, and Role in the Drainage of Fluids and Solutes

Abstract

The cerebral vasculature is made up of highly specialized structures that assure constant brain perfusion necessary to meet the very high demand for oxygen and glucose by neurons and glial cells. A dense, redundant network of arteries is spread over the entire pial surface from which penetrating arteries dive into the cortex to reach the neurovascular units. Besides providing blood to the brain parenchyma, cerebral arteries are key in the drainage of interstitial fluid (ISF) and solutes such as amyloid-beta. This occurs along the basement membranes surrounding vascular smooth muscle cells, toward leptomeningeal arteries and deep cervical lymph nodes. The dense microvasculature is made up of fine capillaries. Capillary walls contain pericytes that have contractile properties and are lined by a highly specialized blood-brain barrier that regulates the entry of solutes and ions and maintains the integrity of the composition of ISF. They are also important for the production of ISF. Capillaries drain into venules that course centrifugally toward the cortex to reach cortical veins and empty into dural venous sinuses. The walls of the venous sinuses are also home to meningeal lymphatic vessels that support the drainage of cerebrospinal fluid, although such pathways are still poorly understood. Damage to macro- and microvasculature will compromise cerebral perfusion, hamper the highly synchronized movement of neurofluids, and affect the drainage of waste products leading to neuronal and glial degeneration. This review will present vascular anatomy, their role in fluid dynamics, and a summary of how their dysfunction can lead to neurodegeneration.

Keywords: cerebral vessel; glymphatic; intramural periarterial drainage; neurodegeneration; perivascular space; small vessel disease.

Figure 1

Diagrammatic summary of the structure of an arteriole in the gray matter. Endothelium hosts the blood–brain barrier. There are several layers of smooth muscle cells separated by basement membranes. Adventitial leptomeningeal sheath has its own basement membrane that fuses with the basement membrane of astrocyte end feet to form a perivascular compartment or perivascular space. Diagram drawn by Marco Fanuli.

Figure 2

(A) The fine anatomy of the cerebral arterial wall. An artery is lined by endothelium (Endo) and coated by the tunica media (TM) composed of smooth muscle cells and by the outermost tunica adventitia (TA) composed of connective tissue. As it enters the brain, the artery loses the tunica adventitia but is still coated by a layer of pia-arachnoid (Pia) that intervenes between the artery and the glia limitans (GL) of the brain. As the arteriole divides into capillaries, the tunica media, and the layer of pia mater are lost. Thus, at the level of the capillary, the GL is in direct contact with the wall of the capillary. (B) Schematic representation of the IPAD and convective influx/glymphatic systems of the brain. On the left-hand side of the diagram, an artery enters the brain from the SAS, and an arteriole divides into capillaries. Tracers in the CSF enter the brain along the pial-glial basement membrane (1) between the pia mater and the GL (indicated by a green arrow) and enter the brain parenchyma and interstitial fluid by an aquaporin four-dependent mechanism, which is the glymphatic pathway (2). On the right-hand side of the diagram, the red arrows indicate the intramural perivascular lymphatic drainage pathway by which interstitial fluid (ISF) and solutes pass out of the brain along basement membranes in the walls of capillaries (3a) and along basement membranes surrounding smooth muscle cells in the tunica media of arterioles and arteries (3b). Reproduced with permission from Morris et al. (90)