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Cipolla MJ. The Cerebral Circulation. San Rafael (CA): Morgan & Claypool Life Sciences; 2009.

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The Cerebral Circulation.

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Chapter 2Anatomy and Ultrastructure

The Arteries

The brain is one of the most highly perfused organs in the body. It is therefore not surprising that the arterial blood supply to the human brain consists of two pairs of large arteries, the right and left internal carotid and the right and left vertebral arteries (Figure 1). The internal carotid arteries principally supply the cerebrum, whereas the two vertebral arteries join distally to form the basilar artery. Branches of the vertebral and basilar arteries supply blood for the cerebellum and brain stem. Proximally, the basilar artery joins the two internal carotid arteries and other communicating arteries to form a complete anastomotic ring at the base of the brain known as the circle of Willis, named after Sir Thomas Willis who described the arterial circle (circulus arteriosus cerebri). The circle of Willis gives rise to three pairs of main arteries, the anterior, middle, and posterior cerebral arteries, which divide into progressively smaller arteries and arterioles that run along the surface until they penetrate the brain tissue to supply blood to the corresponding regions of the cerebral cortex (Figure 2).

FIGURE 1. The internal carotid and vertebral arteries: right side.

FIGURE 1

The internal carotid and vertebral arteries: right side. Reproduction of a lithograph plate from Gray’s Anatomy from the 20th U.S. edition of Gray’s Anatomy of the Human Body, originally published in 1918. It is not copyrightable in the (more...)

FIGURE 2. The arteries of the base of the brain.

FIGURE 2

The arteries of the base of the brain. The temporal pole of the cerebrum and a portion of the cerebellar hemisphere have been removed on the right side. Reproduction of a lithograph plate from Gray’s Anatomy from the 20th U.S. edition of Gray’s (more...)

Cerebral Vascular Architecture

The pial vessels are intracranial vessels on the surface of the brain within the pia–arachnoid (also known as the leptomeninges) or glia limitans (the outmost layer of the cortex comprised of astrocytic end-feet) [1]. Pial vessels are surrounded by cerebrospinal fluid (CSF) and give rise to smaller arteries that eventually penetrate into the brain tissue (Figure 3). Penetrating arterioles lie within the Virchow–Robin space and are structurally between pial and parenchymal arterioles. The Virchow–Robin space is a continuation of the subarachnoid space and varies considerably in depth by species [1]. The penetrating arteries become parenchymal arterioles once they penetrate into the brain tissue and become almost completely surrounded by astrocytic end-feet [2,3].

FIGURE 3. Pial arteries on the brain surface have perivascular nerves that give rise to penetrating arteries within the Virchow–Robin space.

FIGURE 3

Pial arteries on the brain surface have perivascular nerves that give rise to penetrating arteries within the Virchow–Robin space. As penetrating arterioles become parenchymal arterioles within the brain neuropil, they become associated with neurons (more...)

There are several important structural and functional differences between pial arteries on the surface of the brain and smaller parenchymal arterioles. First, pial arteries receive perivascular innervation from the peripheral nervous system also known as “extrinsic” innervation, whereas parenchymal arterioles are “intrinsically” innervated from within the brain neuropil (see Perivascular Innervation). While parenchymal arterioles have only one layer of circumferentially oriented smooth muscle, they possess greater basal tone and are unresponsive to at least some neurotransmitters that can have large effects on upstream vessels (e.g., serotonin, norepinephrine) [4]. Lastly, pial vessel architecture forms an effective collateral network such that occlusion of one vessel does not appreciably decrease cerebral blood flow [5]. However, penetrating and parenchymal arterioles are long and largely unbranched such that occlusion of an individual arteriole results in significant reductions in flow and damage (infarction) to the surrounding local tissue [5].

Despite differences in vessel architecture, all vessels in the brain have endothelium that is highly specialized and has barrier properties that are in some ways more similar to epithelium than endothelium in the periphery. Because of these unique barrier properties that tightly regulate exchange of nutrients, solutes, and water between the brain and the blood, the cerebral endothelium in known as the blood–brain barrier (BBB) [6,7] (see Blood–Brain Barrier).

The Veins

The cerebral venous system is a freely communicating and interconnected system comprised of dural sinuses and cerebral veins [8,9]. Venous outflow from the cerebral hemispheres consists of two groups of valveless veins, which allow for drainage: the superficial cortical veins and the deep or central veins (Figure 4). The superficial cortical veins are located in the pia matter on the surface of the cortex and drain the cerebral cortex and subcortical white matter. The deep or central veins consist of subependymal veins, internal cerebral veins, basal vein, and the great vein of Galen (Figure 5). These veins drain the brain’s interior, including the deep white and gray matter surrounding the lateral and third ventricles or the basal cistern and anastomose with the cortical veins, emptying into the superior sagittal sinus (SSS). Venous outflow from the SSS and deep veins is directed via a confluence of sinuses toward the sigmoid sinuses and jugular veins. The cerebellum is drained primarily by two sets of veins, the inferior cerebellar veins and the occipital sinuses. The brain stem is drained by the veins terminating in the inferior and transverse petrosal sinuses.

FIGURE 4. Superficial cortical veins and dural sinuses.

FIGURE 4

Superficial cortical veins and dural sinuses. Reproduction of a lithograph plate from Gray’s Anatomy from the 20th U.S. edition of Gray’s Anatomy of the Human Body, originally published in 1918.

FIGURE 5. Deep or central veins.

FIGURE 5

Deep or central veins. Reproduction of a lithograph plate from Gray’s Anatomy from the 20th U.S. edition of Gray’s Anatomy of the Human Body, originally published in 1918.

Structure of Cerebral Vessels

The wall of cerebral arteries and arterioles consist of three concentric layers: the innermost layer is the tunic intima, which consists of a single layer of endothelial cells and the internal elastic lamina (IEL); the next layer out is the tunica media, which contains mostly smooth muscle cells with some elastin and collagen fibers; and the outermost layer is the tunica adventitia, composed mostly of collagen fibers, fibroblasts, and associated cells such as perivascular nerves (in large and small pial arteries) and pericytes and astrocytic end-feet (in parenchymal arterioles and capillaries). Unlike systemic arteries, cerebral arteries have no external elastic lamina, but instead have a well-developed IEL [10]. Other differences from systemic arteries include a paucity of elastic fibers in the medial layer and a very thin adventitia. The number of smooth muscle cell layers varies depending on the size of the vessels and species, with large arteries such as the internal carotid artery having as many as 20 layers. Smaller pial arteries contain approximately two to three layers of smooth muscle, whereas the penetrating and parenchymal arterioles contain just one layer of smooth muscle. In addition, smooth muscle in the medial layer of cerebral arteries and arterioles are circularly arranged and oriented perpendicular to blood flow with essentially a zero-degree pitch. Cerebral veins are very thin-walled compared to arteries. The larger pial veins have circumferentially oriented smooth muscle that is not present in veins in the parenchyma. Unlike veins in the periphery, cerebral veins do not contain valves [9].

The Microcirculation and the “Neurovascular Unit”

The capillary bed of the brain is comprised of a dense network of intercommunicating vessels that consist of specialized endothelial cells and no smooth muscle [2]. The total length of capillaries in the human brain is ~400 miles [11]. It is the primary site of oxygen and nutrient exchange, which in turn is dependent on the path length and transit time of red blood cells. In the brain, all capillaries are perfused with blood at all times [12], and it has been estimated that nearly every neuron in the brain has its own capillary [13], demonstrating the critical relationship between the neuronal and vascular compartments. The intravascular pressure gradient between the precapillary arteriole and postcapillary venule is the primary regulator of capillary flow. Dilatation of resistance arteries and arterioles increases the microvascular pressure gradient and increases capillary flow. Thus, regulation of flow in the microcirculation is dependent on the regulation of flow and microvascular pressure in the brain arterioles. Red cell velocity in the cerebral capillary microcirculation is remarkably high (~1 mm/sec) and heterogeneous (range: 0.3 to 3.2 mm/sec) [14]. The heterogeneous flow velocity is important for effective oxygen transport to neuronal tissue that has considerable metabolic needs that fluctuate regularly.

Under normal conditions, the density of brain capillaries varies significantly within the brain depending on location and energy needs with higher capillary density in gray vs. white matter [15]. Pathological, physiological, and environmental states can influence or promote changes in capillary density. For example, chronic hypoxia increases capillary density through activation of angiogenic pathways (e.g., hypoxia inducible factor-1 and vascular endothelial growth factor) driven by a decrease in the driving force of PO2 [16,17]. Brain capillary density nearly doubles between 1 and 3 weeks of chronic hypoxic exposure [16]. This adaptive increase in capillary density during chronic hypoxia increases cerebral blood volume [18] and restores tissue oxygen tension [19]. Hypertension also affects brain capillary density. Similar to the peripheral microcirculation, hypertension causes rarefaction (decrease in number) of capillaries and impaired microvessel formation that can increase vascular resistance [20].

Brain capillary structure is also unique compared to other organs. Endothelial cells and pericytes are encased by basal lamina (~30–40 nm thick) containing collagen type IV, heparin sulfate proteoglycans, laminin, fibronectin, and other extracellular matrix proteins [12,21]. The basal lamina of the brain endothelium is continuous with astrocytic end-feet that ensheath the cerebral capillaries (Figure 6). Astrocytes have a significant influence on capillary function, including regulating cerebral blood flow, upregulating tight junction proteins, contributing to ion and water homeostasis, and interfacing directly with neurons [2,3,12,22,23]. Although the barrier properties of the BBB are at the level of the tight junction in endothelial cells (see Blood–Brain Barrier), there is an important role for other components of the BBB, including the basement membrane, pericytes, astrocytes, and neurons. There is complex cross-talk between all entities and cell types, collectively known as the “neurovascular unit.” Consideration of the neurovascular unit is important for disease processes that induce hemorrhage, vasogenic edema, infection, and inflammation [12,21,22,23]. The neurovascular unit may be the primary site of dysfunction for some disease state; however, for others such as atherosclerosis, large arteries are predominantly affected. For others, such as chronic hypertension, all segments of the circulation are affected.

FIGURE 6. Schematic of the neurovascular unit.

FIGURE 6

Schematic of the neurovascular unit. (A) Endothelial cells and pericytes are separated by the basement membrane. Pericyte processes sheathe most of the outer side of the basement membrane. At points of contact, pericytes communicate directly with endothelial (more...)

Pericytes

Pericytes were discovered in 1890 by Rouget as cells adjacent to capillaries that share a common basement membrane with endothelial cells [24]. The pericyte/endothelia ratio is high in the brain compared to the vasculature of other organs, e.g., 1:3 in brain vs. 1:100 in skeletal muscle [25]. Pericytes can be oriented along a blood vessel or circumvent the vessel with long processes that cover a large part of the abluminal surface. Pericytes have a number of potential roles in the brain, although it has been difficult to define these roles in vivo. They contribute to the stability of the vessel and release growth factors and matrix important for microvascular permeability, remodeling, and angiogenesis [26].

Collaterals

The collateral circulation in the brain consists of vascular networks that allow for maintenance of cerebral blood flow when principal inflow conduits fail due to occlusion or constriction. The circle of Willis at the base of the brain allows for redistribution of blood flow when extracranial or large intracranial vessels are occluded [27,28] (Figure 7). This anastomotic loop provides low-resistance connections that allow reversal of blood flow to provide primary collateral support to the anterior and posterior circulations. However, the anatomy of the circle of Willis varies substantially with species and individuals and is often asymmetric [28].

FIGURE 7. Diagram of the arterial circulation at the base of the brain.

FIGURE 7

Diagram of the arterial circulation at the base of the brain. Reproduction of a lithograph plate from Gray’s Anatomy from the 20th U.S. edition of Gray’s Anatomy of the Human Body, originally published in 1918.

The pial network of leptomeningeal vessels comprises secondary collaterals and are responsible for redistribution of flow when there is constriction or occlusion of an artery distal to the circle of Willis [27]. These vessels comprise distal anastomoses from branches of the anterior, middle, and posterior cerebral pial arteries (Figure 8). The functional capacity for collateral supply is dependent on the number and luminal caliber of the vessel that can be quite variable in the leptomeningeal anastomoses. Venous collaterals exist as well to augment drainage when primary routes are occluded or during venous hypertension [28]. The superficial cerebral veins are highly anastomosed with each other to provide a network of collaterals [8]. The deep veins are anastomosed with other venous systems and also provide collateral support for drainage [8].

FIGURE 8. Collateral circulation of the brain.

FIGURE 8

Collateral circulation of the brain. Heubner’s leptomeningeal anastomoses connect the peripheral branches of the brain arteries and provide collateral blood flow to the peripheral parts of the adjacent vascular territories. Used with permission (more...)

Copyright © 2010 by Morgan & Claypool Life Sciences.
Bookshelf ID: NBK53086

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