2017 Brain Circulation Published by Wolters Kluwer Health Medknow 45The cerebral circulation and [627491]

© 2017 Brain Circulation | Published by Wolters Kluwer Health – Medknow 45The cerebral circulation and
cerebrovascular disease I: Anatomy
Ankush Chandra1, William A Li1, Christopher R Stone1, Xiaokun Geng1,2,
Yuchuan Ding1
Abstract:
In this paper, which is the first in a three‑part series that reviews cerebrovascular anatomy, pathogenesis,
and stroke, we lay the anatomical foundation for the rest of the series. Beginning with its origin in the
branches of the aorta, we start by describing the arterial system. This system is partitioned into two
major divisions (anterior and posterior circulations) that differ significantly in features and pathogenic
potential. The systems, and the major branches that comprise them, are described. Description of
the arterial system proceeds to the point of the fulfillment of its function. This function, the exchange
of gases and nutrients with the cerebral parenchyma, is the subject of a subsequent section on the
microcirculation and blood–brain barrier. Finally, the cerebral venous system, which is composed of
cerebral veins and dural venous sinuses, is described. Thus, an anatomical context is supplied for
the discussion of cerebrovascular disease pathogenesis provided by our second paper.
Keywords:
Cerebral arteries, cerebral circulation, cerebral microcirculation, blood brain barrier, cerebral venous
system, cerebrovascular anatomy, cerebrovascular disease
Origin of the Cerebral Circulation
While the brain is 2% of the total body
mass, it uses nearly 50% of the
human body’s glucose. This makes it the
most energy-intensive organ of the human
body.[1] Thus, it follows straightforwardly
that the brain ought also to be one of
the most perfused organs in the body,
which, indeed, it is. Two major sources
of arterial blood provide this perfusion:
the anterior circulation that originates
in the internal carotid arteries [Figure 1]
and the posterior (or vertebrobasilar)
circulation that originates in the vertebral
arteries [ Figure 2]. Once these arteries enter
the cranium, they branch exuberantly,
eventually supplying blood to all deep and
superficial regions of the brain. Perturbation
of any portion of this blood supply, whether
intracranially or extracranially, promotes
the development of cerebrovascular diseases, the most common and notorious
of which is stroke.
Just like the circulation to the rest of the
body, the cerebral circulation originates
in the left heart and is conducted by the
aorta. The conduction of blood begins
during systole, with the left ventricular
ejection of oxygenated blood into the
aorta. As the aorta ascends, it becomes
the ascending aorta and subsequently
forms the aortic arch, which gives rise
to three branches.[2] The first and largest
branch is the brachiocephalic trunk, which
originates behind the manubrium; the
second branch is the left common carotid
artery, which originates to the left of the
brachiocephalic trunk; and the third is the
left subclavian artery, which ascends with
the left common carotid artery through the
superior mediastinum and along the left
side of the trachea.[2]
The vertebral arteries arise as the most
proximal ascending branch from the Address for
correspondence:
Dr. Xiaokun Geng,
Department of Neurology,
Beijing Luhe Hospital,
Capital Medical University,
No. 82, Xinhua South
Road, Tongzhou District,
Beijing 101149, China.
E‑mail: xgeng@ccmu.
edu.cn
Submission: 10‑03‑2017
Revised: 28‑05‑2017
Accepted: 07‑06‑20171Department of
Neurological Surgery,
Wayne State University
School of Medicine,
Detroit, MI, USA,
2Department of Neurology,
Beijing Luhe Hospital,
Capital Medical University,
Beijing, ChinaAccess this article online
Quick Response Code:
Website:
http://www.braincirculation.org
DOI:
10.4103/bc.bc_10_17
How to cite this article: Chandra A, Li WA,
Stone CR, Geng X, Ding Y. The cerebral circulation
and cerebrovascular disease I: Anatomy. Brain Circ
2017;3:45‑56.Review Article
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Chandra, et al.: Cerebral circulation: Anatomy46 Brain Circulation ‑ Volume 3, Issue 2, April‑June 2017subclavian arteries on each side of the body and enter
deep into the cervical vertebral transverse processes,
typically at the level of the 6th cervical vertebra, but
about 7.5% of the time at the level of C7.[3] Other
variations in the vertebral arterial route have also been
noted, including anomalies in intraforaminal position,[4]
and in length of the looped segment between C2 and
the dura mater pierce point. Although uncommon,
some of these variations may be of considerable
surgical or pathophysiological relevance. It is thought,
for example, that a sufficiently short loop segment
can predispose patients to fatal traumatic basal
subarachnoid hemorrhage.[5] Typically positioned or
otherwise, the arteries in any case proceed superiorly
in the transverse foramen of each cervical vertebra,
ultimately passing through the transverse foramen
of the atlas (C1). Once here, they make a sharp
posterior bend, traveling across the posterior arch
of C1 and through the suboccipital triangle, piercing
the dura mater on their way toward the foramen
magnum.[2] Passage through the foramen magnum
marks the beginning of the arteries’ intracranial course,
which constitutes the incipient segment of the posterior
cerebral circulation and will be detailed in a subsequent
section of this paper.
Whereas the vertebral arteries are bilaterally symmetrical
in course, marked lateral variation in the origin of the
common carotid arteries is characteristic of human
anatomy. While the left common carotid artery arises
directly from the aortic arch, the right internal carotid
artery (ICA) arises from the brachiocephalic trunk.[6] The
first and largest branch of the arch, the brachiocephalic
trunk, originates on the right side of the chest near the
trachea, and bifurcates posterior to the sternoclavicular
joint into the right subclavian artery and right common
carotid artery as it moves rightward within the superior
mediastinum. On the left side of the body, however, there is no brachiocephalic trunk: on this side, the
common carotid artery comes directly from the aortic
arch as its second branch.[7] Despite this variation in
origin, the common carotid arteries then pursue a
symmetrical ascent in the chest, ending as they split into
the internal and external carotid arteries at the superior
border of the thyroid cartilage, at around the level of
fourth cervical vertebra.[2] Unlike the external carotid
arteries, the internal carotid arteries do not give off any
branches in the neck. The only task of these vessels is
to supply the brain’s anterior circulatory system, which
they begin to do after entering the cranial cavity just
anteriorly to the jugular foramen, through the carotid
canal.
Anatomy of the Cerebral Circulation
To begin with its simplest anatomical classificatory
scheme, the cerebral circulation is composed of a
supplying arterial circulation and a draining venous
circulation. The arterial system can then itself be
subdivided according to anatomical position, into
anterior and posterior cerebral circulations, as has been
discussed. One can also divide the arterial circulation
by size. According to this scheme, the macrocirculation
may be considered to comprise the gross branches
of the cerebral vascular responsible for the regional
perfusion of the cerebrum. The microcirculation is then
derivatively defined as the microscopic site of oxygen
and nutrient exchange within the vasculature, as well as
of the blood–brain barrier (BBB).[8] Continuing with the
anatomical scheme, the microcirculation is terminally
productive of the brain’s venous circulation: a freely
communicating, interconnected system of dural venous
sinuses and cerebral veins.[9,10] Although the venous
system is often given less attention than its arterial
counterpart (likely due to the relevance of the latter to
the topic of ischemic stroke), it should not be forgotten
that it, too, can serve as a significant focus of cerebral
pathology, as is described below. Beginning with the
arterial supply, we will discuss each of these circulatory
systems in detail.
Figure 1: Anterior circulation: Left and right internal carotid arteries as seen with
angiography
Figure 2: Posterior circulation: Left and right vertebrobasilar artery system as seen
with angiography
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Chandra, et al.: Cerebral circulation: AnatomyBrain Circulation ‑ Volume 3, Issue 2, April‑June 2017 47The Arterial System
Following their entry into the cranial cavity, the internal
carotid and vertebral arteries fulfill the formidable
role of exclusive suppliers of the blood necessary to
maintain the brain, and all its many crucial functions,
in working order (note that this is not the only function
served by these enormously important vessels; the
arterial networks also drain interstitial fluid and protein
from the brain).[11] It has already been mentioned that
the carotids are the major conduit for blood,[12] but the
vertebral supply should not therefore be discounted.
Before and after anastomosing to form the single,
midline basilar artery, the vertebral vessels represent the
primary supply of blood to the brainstem; compromise
of this system can thus entail catastrophic consequences
related to disruption in the critical brainstem autonomic
centers. By contrast, both circulatory divisions provide
major branches to the diencephalic and telencephalic
regions of the brain proper. To do so, the circulations
first meet as the Circle of Willis [Figure 3]: an arterial
wreath, located approximately within the brain’s
interpeduncular fossa, and surrounding the optic chiasm.
Initially described by Thomas Willis in 1664, the circle is
a salient anatomical landmark of considerable anatomic
variability. Variability notwithstanding, it is in any case
the critical anastomotic junction between the internal
carotid and vertebral artery supply to the brain, from
which the rest of the major branches stem. It therefore
occupies a very important position in the collateral
pathway of cerebral arteries. This becomes especially
important in ischemic conditions, under which variation
can predispose patients to pathology. For example,
a study of 976 atherosclerotic patients found that an
incomplete anterior Circle of Willis, present in 23% of the
study population, carries a hazard ratio of 2.8 for future
anterior circulation ischemic strokes.[13] In addition, it has
been proposed that demographic variation in this arterial wreath may partially explain the different incidence of
some varieties of cerebrovascular diseases in different
racial groups.[14]
The branches of the circle are as follows: the anterior
cerebral artery (ACA), anterior communicating
artery (ACoA), ICA, posterior cerebral artery (PCA),
posterior communicating artery (PCoA), and basilar
artery.[15] From their origin within the interpeduncular
fossa, these branches course centrifugally toward their
divergent cerebral targets, becoming the cerebral arteries
that are grossly visible covering the cortical surface (also
known as leptomeningeal arteries), or ending as
perforating or choroidal branches to deeper structures.[16]
We will not treat these tiny and numerous terminal
branches in any detail, but, since it is indispensable
to a working appreciation of normal neurovascular
function, we will discuss each of the larger branches
in detail. Moreover, an understanding of the course
of (and structures supplied by) these vessels is also
the foundation necessary to localize and treat stroke,
which will be the subject of our follow- up paper.[17]
In this paper, they will be presented according to the
anatomical classificatory scheme, beginning with the
anterior circulation.
The Anterior Cerebral Circulation
The anterior cerebral circulation is composed of branches
from the ICA. There are many such branches, but the
ACA, middle cerebral artery (MCA), and the anterior
choroidal artery (AChA) are highly prominent and
pathophysiologically significant. Overall, the function
of the anterior division of the cerebral circulation is
to supply blood to a large proportion of the forebrain,
including the frontal, temporal, and parietal lobes, as
well as parts of the diencephalon and internal capsule.
The contribution of the anterior circulation to total
cerebral blood flow has been measured by phase‑contrast
magnetic resonance imaging (MRI) at 72%.[18]
Anterior cerebral artery
The ACA primarily supplies blood to the most medial
aspect of the cerebral cortical surface, located along
the longitudinal fissure that divides the brain’s two
hemispheres. This area includes portions of the frontal
lobes, as well as the superomedial parietal lobes;
because it ends rostral to the parieto-occipital sulcus,
this artery does not supply the medial occipital lobe.
Its course is as follows: after arising from the anterior
clinoid portion of the ICA, it courses anteromedially
over the superior surface of the optic chiasm, toward the
longitudinal fissure. Shortly after arrival in the fissure,
it forms an anastomosis with the contralateral ACA.
This anastomosis is called the anterior communicating
artery. While small, this artery is nevertheless the most
Figure 3: Circle of Willis as seen with magnetic resonance angiography
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Chandra, et al.: Cerebral circulation: Anatomy48 Brain Circulation ‑ Volume 3, Issue 2, April‑June 2017common location of (36%) of cerebral aneurysms and
is thus of enormous pathological importance.[19] It also
marks the first segmental division of the ACA, which is
divided regionally into five segments along its course:
A1–A5. Table 1 describes these segments, their major
branches, the structures they supply, and the significance
of any anatomical variation associated with them. As the
ACA proceeds, then, beyond A1, it begins its posterior
course toward the parieto -occipital sulcus, following the
contour of the callosal sulcus between the two cerebral
hemispheres. Throughout this whole course, the ACA
provides deep and cortical branches; these arise from the
proximal and distal portions of ACA, respectively.[30,31]
Anterior choroidal artery
AChA is a branch of the ICA that typically arises from
the supraclinoid portion, just before the bifurcation of
the middle and anterior cerebral arteries.[32] However,
many anatomical variations have been found: AChA
has also been found to originate from the MCA or even
from the PCoA.[33,34] Although rare, still other variations
have also been observed, including complete absence,
as well as duplication, of AChA.[35,36] As should hardly
be surprising given this variety of possible courses, the
vascular territory of the AChA has been a matter of
debate in recent years. Whatever its course, however,
the AChA gives off both deep and superficial branches.
The vascular territory of the deep branches includes the
posterior two-thirds of the internal capsule, adjacent
optic and auditory radiations, medial portion of the
globus pallidus, and tail of the caudate nucleus; the
territory of the superficial branches includes piriform cortex and uncus, hippocampal head, amygdala, and
most lateral portion of the thalamic lateral geniculate
nucleus.[32,37-40]
Middle cerebral artery
MCA is the largest and most complexly distributed of
the cerebral vessels, supplying many critical cerebral
structures along its sinuous course.[41] Neither that the
MCA is the most common site of stroke,[42] nor that
large-territory MCA strokes often carry a very poor
prognosis,[43] should therefore come as a surprise. The
artery has a relatively consistent route: variations have
been found in 3.8% of patients, and have not been
determined to be of clinical significance.[44] It originates
from the bifurcation of the ICA, just lateral to the optic
chiasm at the medial end of the Sylvian fissure,[3,33] and
passes laterally from there along the ventral surface of
the frontal lobe, entering the Sylvian fissure between
the temporal lobe and insular cortex. Within this region,
the artery typically bifurcates or trifurcates, giving rise
to two or three principal trunks. These, in turn, extend
superiorly and inferiorly over the insular surface,
supplying, by means of an arterial arborization that
ultimately extends over most of the lateral surface of the
cerebral hemisphere, the following cortical territories:
all of the insular cortex and opercular surface, the
superior and middle temporal gyri, a parietal territory
that comprehends the inferior parietal lobule and much
of the postcentral gyrus, and a frontal territory that
comprehends inferior and middle frontal gyri, much of
the precentral gyrus, and the lateral part of the orbital
surface. Just as has been seen above for the sake of
Table 1: Anterior cerebral artery segments and their blood supply
Segment Boundaries Branches Regions supplied Important variants
A1 Between ICA and ACoA Medial lenticulostriate artery; ACoA;
small arterial branches to perforated
substance, subfrontal area, dorsal
surface of optic chiasm, hypothalamus,
and suprachiasmatic nucleus[20]Caudate nucleus and
anterior limb of the
internal capsule, anterior
hypothalamus, septum
pellucidum, anterior
commissure, fornix, and
the anterior striatum[21]Fenestrated A1: Rare,
it is associated with
aneurysms[22‑24]
A2 ACoA to the bifurcation
forming the pericallosal
and supramarginal
arteriesRecurrent artery of Heubner (may also
arrive from A1, rarely),[25] orbitofrontal
artery and frontopolar artery, small
arterial branches to perforated
substance, subfrontal area, dorsal
surface of optic chiasm, hypothalamus,
and suprachiasmatic nucleus[3]Anterior portion of
caudate nucleus, Internal
capsule, inferior and
inferomedial surfaces of
the frontal lobe including
gyri recti[9]Superior anterior CoA: An
anomalous communicating
vessel between the ACAs
near the corpus callosum
has been associated with
aneurysms (book)
(ii) Azygos ACA: Associated
with terminal aneurysms[26‑27]
and holoprosencephaly[28]
A3 (pericallosal
artery)Pericallosal sulcus,
extends around genu of
corpus callosumSuperior and inferior internal parietal
arteries, precuneal artery, callosal
marginal artery (present only in 60%
of cases)[25]Corpus callosum,
superior frontal gyrus,
precuneus, and medial
aspect of hemisphere
above corpus callosum[29]Contralateral hemisphere
supply: In about 64% of
people, A3 has branches
supplying the contralateral
hemisphere[30]
A4 and A5[5‑8]Smaller branches that
go over corpus callosumCallosal arteries (smaller arteries) Corpus callosum
ACoA: Anterior communicating artery, ICA: Internal carotid artery, ACAs: Anterior cerebral arteries
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Chandra, et al.: Cerebral circulation: AnatomyBrain Circulation ‑ Volume 3, Issue 2, April‑June 2017 49rendering a large and sinuous vascular route more
comprehensible in the case of the ACA, these many
MCA territories have been partitioned into segments.
The names of these segments, their paths, branches, and
the structures they supply are shown in [ Table 2].
The Posterior Cerebral Circulation
Although it provides only about one-third of the total
flow perfusing the brain, the posterior cerebral circulation
still maintains many of the nervous system’s most critical
functions. Also known as the vertebrobasilar circulation,
it is comprised of the vertebral arteries, the basilar artery
into which the vertebrals fuse, and several branches
from these main conduits to be detailed below.[36] This
circulation may be broadly considered to supply blood
to the posterior portion of the brain that includes the
occipital lobe, most of the anterior and posterior portions
of the brainstem, and all of the cerebellum.[3,36] Beginning
with its origin in the vertebral arteries, we will now
provide an anatomically organized overview of this
circulatory division. Because it is a less frequent focus of
cerebrovascular pathology, accounting for only 20% of
ischemic strokes,[48] our survey will be brisker than what
was presented of the anterior circulation. Nevertheless,
there are many features of pathological interest in this
circulation, and they will be described below.
Vertebral arteries
As introduced above, these are paired, bilaterally
symmetrical arteries that arise from the subclavian
vessels on each side of the body. Like the MCA, they
have been partitioned, for the sake of organizational
clarity, into four segments. Unlike MCA, the first three of these segments are extracranial. The most proximal
segment, V1, extends from the vessels’ subclavian
origin to the vertebral transverse foramen, and is, along
with the distal V4, the most common site of vertebral
artery infarction.[49] The succeeding V2 segment then
courses through the transverse foramen. V3, which
has already been discussed for the predisposition to
hemorrhage possessed by its shortened variations, loops
from approximately the level of C2 around the atlas
and then enters the dura. Once through the dura, the
arteries become V4 – this is the intracranial segment of
the vertebral arteries. Running from its dural entrance
to the rostral medulla or caudal pons, this segment
has many vascular tasks. Immediately after entering
the brain through the foramen magnum and prior to
its anastomosis at the caudal pontine level, it gives
rise to two important branches. The first of these is the
posterior inferior cerebellar artery (PICA).[36] Second,
and immediately proximal to the anastomosis, each V4
gives rise to a small branch that joins its contralateral
counterpart to form the descending, midline anterior
spinal artery. There is also a set of posterior spinal
arteries. These may arise either from PICA or from the
vertebral arteries, but will not be discussed further, due
to the relatively small brainstem territory they supply,
as well as the rarity and variability characteristic of
lesions in these vessels.[50] There are, by contrast, several
structural and functional features of PICA and the
anterior spinal artery that bear discussion. These are
now summarized.
Posterior inferior cerebellar artery
PICA is the largest branch of the vertebral artery.
After splitting off from its vertebral origin, it winds
Table 2: Middle cerebral artery segments and their supply
Segment Anatomical path Branches Areas supplied
M1 (horizontal) Originates at carotid bifurcation, becomes
middle cerebral artery, and branches turn
superiorly into the area between temporal
lobe and insulaMedial and lateral lenticulostriate
arteries (15‑17 in number) and
anterior temporal arteryHead and body of the caudate nucleus, the
upper part of the anterior limb, the genu
and anterior portion of the posterior limb
of internal capsule, the putamen and the
lateral pallidum and anterior temporal lobe
M2 (insular) Entry point at temporal lobe and insula,
ascends along the insular cleft and
makes a hairpin turn at the insular sulcusTerminal branches: 2‑3 main trunks
Superior division: Orbitofrontal
artery, prefrontal artery, precentral
artery, and central arteries
Inferior division: Temporopolar
artery, temporo‑occipital artery,
angular artery and anterior, middle
and posterior temporal arteriesSuperior division: Orbitofrontal area to the
posterior parietal love
Inferior division: Temporal pole to the
angular area of parietal lobe
M3 (opercular) Begins at the apex of the hairpin turn in
the insular sulcus and terminates as the
branches reach the lateral convexity of
the cerebral hemisphereTerminal branches/2‑3 main trunks:
Upper and lower trunksFrontal, parietal, and temporal operculae
M4 (cortical) Begins at the surface of the Sylvian
fissure, extends over cerebral
hemisphere and arises between frontal,
parietal and temporal lobes[3,35]Cortical branches Hemispheric surface of frontal and parietal
lobes[45]
Derived from[3,46,47]
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Chandra, et al.: Cerebral circulation: Anatomy50 Brain Circulation ‑ Volume 3, Issue 2, April‑June 2017posteriorly around the upper medulla, passes between
the origins of the vagus and accessory nerves, and
then proceeds along the inferior cerebellar peduncle
to reach the ventral surface of the cerebellum, where
it divides into medial and lateral branches. The
artery provides blood to the part of the medulla and
cerebellum corresponding to its course: the dorsolateral
region of the medulla and a region of the ventral
surface of the cerebellar hemispheres that includes
the inferior vermis.[3,36] PICA lesions produce the
symptoms consistent with this distribution, including
ipsilateral loss of facial pain and temperature sensation,
contralateral loss of the same in the body, cerebellar
ataxia, and bulbar palsy. This collection of symptoms
composes the classical neurological syndrome known
as Wallenberg’s syndrome.[51]
Anterior spinal artery
As already discussed, the anterior spinal artery arises
as a midline anastomosis of two small branches from
the vertebral arteries. From this anastomosis, the
artery proceeds within the anterior median fissure
down the whole length of the spinal cord. Before doing
so, however, it rests on and supplies a region in the
anterior medulla. Consequently, like PICA, anterior
spinal artery lesions are associated with a characteristic
neurological syndrome, with symptoms consistent
with hypoperfusion of the medullary regions normally
supplied by this vessel.[52]
Basilar artery
After its anastomosis at the pontomedullary junction, the
paired V4 segments give way to a single, massive basilar
artery that travels along the midline anterior pons,
and terminates near the pontomesencephalic junction.
During its course, the artery branches prolifically,
providing several perforating arteries (classified by
distribution as either paramedian or circumferential) to
the pons, the anterior inferior cerebellar and superior
cerebellar arteries (AICAs and SCAs, respectively) to a
broad cerebellar territory, and then supplies much of the
posterior cortical surface through its terminal split into
the posterior cerebral arteries (PCAs).[3,36,39] As is readily
appreciable due to the vastness of this vascular area,
lesions of the basilar artery are, although uncommon,
very grave in prognosis: a mortality rate of 85% has
been reported of basilar artery occlusions.[53] The
symptomology of survivors, moreover, can also be quite
grave. A condition known as locked-in syndrome can
occur, in which patients are quadriplegic and incapable
of either speech or horizontal eye movements, but are
nevertheless conscious.[54] Lesions of individual basilar
branches can also, of course, occur, giving rise to a
clinical presentation circumscribed to the function of
the affected region. We briefly discuss the distribution
of these branches.Perforating branches of the basilar artery (pontine
branches)
These arteries are small, numerous, basilar branches
that collectively provide a substantial contribution to
the complex vascular territory of the pontine brainstem.
When categorized according to distribution, they fall into
two classes. The first class, referred to as paramedian,
extends immediately from the basilar artery into the
substance of the pons and supplies structures located
relatively close to midline, such as the corticospinal tract.
The second class is called circumflex, due to its more
lateral distribution, which extends its longest branches
all the way around to the dorsal aspect of the pons as
posterior pontine arteries.[55,56]
Anterior inferior cerebellar artery
This artery is the first large branch of the basilar artery
and has an analogous direction of course to the more
caudally positioned PICA. It generally proceeds from
the caudal one-third of the basilar artery, traveling
laterally along the middle cerebellar peduncle to reach
the cerebellum. In addition to typically supplying the
petrosal surface of the cerebellum,[57] it also supplies a
subregion of the pontine brainstem that includes the
middle cerebellar peduncle,[56] and the central portions of
several sensory pathways, as evidenced by the ability of
AICA lesions to mimic schwannomas of the vestibular,
facial, and trigeminal nerves. AICA also usually gives
rise to the labyrinthine artery of the inner ear, which
perhaps helps account for the deafness lesions in this
artery can also produce.[58,59]
Superior cerebellar artery
This artery may be thought of as, like AICA, another
PICA analog. The final, nonterminal branch of the basilar
artery, SCA runs laterally over the superior cerebellar
peduncle, supplying the peduncle itself and, by way
of spreading medial and lateral branches, much of
the superior surface of the cerebellum. It also supplies
the deep nuclei embedded within the cerebellar white
matter, and a brainstem region adjacent to the rostral
pontine tegmentum.[56,59]
Posterior cerebral artery
The final posterior circulation contribution to consider
is that provided by the posterior cerebral arteries. These
arteries usually arise bilaterally from the terminal
bifurcation of the basilar arteries but have been
found to originate unilaterally at the ICA in between
11% and 29% of cases examined. This is a clinically
consequential variant: it can mimic cerebrovascular
pathology on perfusion MRI due to an asymmetric
signature.[60] In any case, after splitting from the basilar
artery or otherwise, the PCA encircles the midbrain at
the pontomesencephalic junction, immediately rostral
to the root of the third (oculomotor) cranial nerve.
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Chandra, et al.: Cerebral circulation: AnatomyBrain Circulation ‑ Volume 3, Issue 2, April‑June 2017 51Along its posterior passage, it travels over the cerebral
peduncles, and thence to the ventromedial surface of the
cortex, thus through an elaborate pattern of branches
constituting a major source of blood to the occipital
lobe, the inferior and medial parts of the temporal lobe,
and a posterior portion of the inferior parietal lobe. As
has been the case in every example mentioned above,
the cortical symptoms produced by PCA infarcts are
consistent with the functions of the artery’s territory:
most commonly (84%–100%), such infarcts produce
visual field deficits, but alexia and agnosias can also
occur, such as, owing to fusiform gyrus dysfunction,
prosopagnosia.[61,62] PCA also has a substantial subcortical
territory that covers the thalamus, midbrain, and choroid
plexus; deep areas have been found to be involved in
almost 30% of pure PCA infarcts.[63] Like the ACA and
MCA of the anterior circulation, the PCA has been
divided into segments by location along its extent, but
we will not discuss these further. The interested reader
may refer to our sources.[40,41,59]
The Microcirculation and Blood–brain
Barrier
Having broadly overviewed the macrocirculatory
components of the cerebrovascular system, we proceed
now to discuss the cerebral microcirculation. Recall that
the microcirculation was defined above as the endpoint
interface of the macrocirculation with the cerebrum:
the site of the exchange of gases and nutrients that
accomplishes the formidable task of maintaining
the totality of cerebral function in working order. In
this section, we will first discuss the main structural
components that make this exchange possible. This
requires the detailed description of the BBB presented,
which includes presentations of the mechanisms by
which the transport of water and other molecules to the
cerebrum is regulated. In Part II of our review series,
we will draw upon the microcirculatory anatomy
presented here for an account of the paradigmatic
consequence of microcirculatory dysfunction: cerebral
edema.[64]
Microcirculatory Function
Neuronal activity is, of course, intimately linked with
cellular metabolism and cerebral blood flow: even minor
interruptions in flow through the cerebrovascular system
can adversely affect cognitive function.[65] The whole
cerebrovascular system is thus subjected to the tight
regulation necessary to ensure concordance between
neuronal metabolic needs, on the one hand, and the blood
flow that underwrites these needs, on the other.
The brain’s microcirculatory system is at the core of its
regulatory apparatus. This system spans the arterial and venous circulations and consists of three components:
parenchymal arterioles (diameter 30 µm; wall thickness
6 µm), capillaries (diameter 8 µm; wall thickness 0.5 µm),
and venules (diameter 20 µm; wall thickness 1 µm). The
capillary bed that intervenes between the system’s two
ends consists of the dense network of miniscule vessels
that represents the primary site of oxygen, nutrient, and
metabolite exchange. Flow through this central region is
regulated by muscular actions at its arterial and venous
ends: contraction and dilation of precapillary arterioles
and postcapillary venules. By this mechanism, flow
through the capillaries is made highly dynamic, capable
of velocities ranging from 0.3 mm/s to 3.2 mm/s.[66,67]
The resultant heterogeneity in capillary flow of which
the system is capable reflects the importance of local
regulation. Unfortunately, this tightly regulated system
is prone to injury, especially during cerebral ischemia.
Due to its role in several cerebral diseases (including
cerebral ischemia), the BBB is arguably the most
important component of the microcirculatory system.
It is certainly the most studied. The BBB is present
throughout the microcirculation’s regulatory system, in
the arterioles, capillaries, and venules described above.
It is both a selective barrier and a transport apparatus,
formed chiefly by endothelial cells that are interlocked
by tight junctions and buttressed by pericytes, astrocytes,
and a basal lamina; most of the transport it facilitates
occurs by the way of a transcellular route through its
endothelial cells. Small gaseous molecules (such as O2
and CO2) and small lipophilic agents (such as barbiturates
and ethanol) simply diffuse through the lipid membrane
of these cells.[68] Transport of hydrophilic molecules,
on the other hand, is controlled as it is peripherally: by
specific endothelial transporters [Figure 4]. In contrast
BLOOD VESSEL
BRAIN PARENCHYMAEndotheliumPassive diffusio n
small lipid-soluble
moleculesReceptor-mediate d
transport
proteins an d
peptide sParacellula r
transport
water-soluble
molecule sCarrier-mediate d
transport
water, ions, glucos e
Figure 4: The regulation of transport across the blood–brain barrier
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Chandra, et al.: Cerebral circulation: Anatomy52 Brain Circulation ‑ Volume 3, Issue 2, April‑June 2017to the endothelia of other organ systems, however,
the cerebral endothelium has a much lower degree of
endocytotic and transcytotic activity.[69] It also expresses
lower levels of leukocyte adhesion molecules than are
seen in peripheral endothelia. This helps inhibit immune
cell infiltration into healthy central nervous system
parenchyma.[70]
In the context of selective transport, it is important to
highlight the role of tight junctions. Tight junctions
confer low paracellular permeability and are vulnerable
to damage during primary cerebral ischemia, and also
during the secondary inflammatory response that
follows primary ischemia. Tight junctions are composed
of adhesion molecules-1,[71] occludins,[72-74] claudins,[75]
and membrane-associated guanylate kinase-like
proteins (ZO-1, ZO-2, and ZO-3).[76] ZO-1, because it
links transmembrane proteins of the tight junction
to the endothelial cytoskeleton, plays an especially
important role in the pathogenesis of cerebral edema.
The dissociation of ZO-1 is associated with increased BBB
permeability.[77,78] In addition to tight junctions, pericytes,
astrocytes, and a basal lamina also serve to stabilize the
BBB, as noted above. Pericytes regulate BBB permeability,
angiogenesis, metabolite clearance, and capillary blood
flow.[79,80] The extracellular matrix, comprised fibronectin,
laminin, and type IV collagen, serves as an anchor for
the endothelium, playing a key role in BBB integrity.[81-83]
Astrocytes stabilize the BBB, closing the gaps between
tight junctions.[84,85] Furthermore, astrocytic end feet
contain high concentrations of surface transporters and
receptors that regulate the brain’s extracellular solute
concentration and water content. This is critical to the
formation and resolution of cerebral edema.
The Cerebral Venous System
Once it proceeds through the capillary beds of the
cerebral microcirculation, and is modified according to
the demand set by cerebral metabolism (that is, stripped
of O2 and nutrients and loaded with CO2 and metabolites),
cerebral blood enters the venous circulation. Continuing
along our anatomically organized tour of the cerebral
circulation, we will now therefore discuss this circulation.
The structures that compose this circulation show
greater anatomical variations than the brain’s arterial
structures. Cerebral veins often differ not only between
individuals but also between the two hemispheres
in the brain of a single individual. This high degree
of variability makes the classification of the cerebral
veins difficult. Nevertheless, some general patterns
can be described, and understanding these patterns
is crucial for determining and treating intracranial
pathologies (e.g., cerebral venous thrombosis [CVT] and
brain tumor) related to these structures. Thus, they are
reviewed below, and central venous thrombosis is briefly presented as a pathological process that illustrates the
distinct physiological properties of the venous system.
The cerebral venous system can be divided into two
anastomosing networks according to position with
respect to the cortical surface: the more superficially
located dural venous sinuses, and the deeper cerebral
veins.[86] Dural venous sinuses are endothelially lined
channels, the general function of which may be considered
the collection of venous blood from the cerebral veins,
and the delivery of this blood to the systemic venous
circulation.[59,87] They are usually formed between the
outer (periosteal) and inner (meningeal) layers of dura
mater, located adjacent to the osseous surfaces inside
the cranium. The confluence of sinuses (CS) is one of the
major sinuses, and may be thought of as a pooling point
for venous blood destined, by the way of carotid bulb,
for the systemic circulation. It is located at the occipital
pole of the cranial cavity and is formed by the junction
of several of the other sinuses. These include the superior
sagittal sinus that runs along the calvaria through the falx
cerebri; the straight sinus that represents the continuation
of the inferior sagittal sinus and great cerebral vein of
Galen;[9] the occipital sinus just inferior to the CS; and the
transverse sinuses that, by way of the sigmoid sinuses,
traverse the base of the occipital bone to connect the CS
with the jugular blub.[87] The inferior sagittal sinus runs
in the inferior concave free border of the cerebral falx,
thus constituting an exception to the general rule that the
sinuses are composed of both meningeal and periosteal
dura. As mentioned, this sinus continues as the straight
sinus, running between the falx cerebri and tentorium
cerebelli to join the CS.
Another important component of the dural sinus
system is composed by the bilateral cavernous sinuses.
Located superior to the body of the sphenoid bone and
demarcated by the superior orbital fissure anteriorly, the
temporal bone posterity, and the sella turcica medially,
these sinuses receive blood from the superior and inferior
ophthalmic veins, superficial middle cerebral veins,
sphenoparietal sinuses, and inferior cerebral veins.[88]
Because they also serve as major pooling points and
are also in communication with the jugular vein, these
sinuses may be conceived as the anterior equivalents
of the occipitally located CS. Two intercavernous
sinuses (an anterior and a posterior) connect the two
cavernous sinuses across the midline. Two sets of
petrosal sinuses then drain the cavernous sinuses: the
superior petrosal sinuses exit posteriorly, and travel
superiorly along the petrous part of the temporal
bone to connect with the sigmoid/transverse sinuses,
while the inferior petrosal sinuses exit inferiorly, and
traverse the petrobasilar suture to drain directly into the
internal jugular veins.[87] The inferior petrosal sinuses are
interconnected by the basilar venous plexus. The sigmoid
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Chandra, et al.: Cerebral circulation: AnatomyBrain Circulation ‑ Volume 3, Issue 2, April‑June 2017 53sinus is a continuation of the transverse sinuses that
passes inferiorly in an “S”-shaped groove posteromedial
to the jugular foramen, and serves to channel cerebral
venous blood to the internal jugular vein.
Despite the impression that the preceding description
may have given, however, the internal jugular vein is
not the only manner by which the dural sinus system
communicates with the extracranial venous system.
There are many emissary veins that serve this purpose,
permitting anastomosis between the extracranial veins
of the face and scalp. These anastomoses are clinically
significant: because the emissary veins lack valves, they
permit the retrograde flow of blood from superficial
structures into the brain, thus permitting superficial
infections to cause infections of the brain.[89] Other
channels exist as well. The vertebral venous plexus, for
example, receives blood from both the inferior petrosal
sinus and the occipital sinus.[9,87]
While the dural sinus system may be broadly understood
as the outlet for cerebral venous blood, it is the cerebral
veins that directly drain the brain’s parenchyma. Once
they have done so, they then pierce the meninges and
continue as bridging veins into the cranial venous
sinuses to exit the cranial cavity as described above. The
cerebral veins can be divided into superficial (cortical)
cerebral veins, and deep (cerebral) veins. The superficial
cerebral veins course along the cortical sulci and drain
the cortex of the brain. Most cortical veins are unnamed;
exceptions are made, however, for a few large cortical
veins that anastomose directly with the sinus system,
such as superficial middle cerebral veins, superior and
inferior anastomotic veins, and superior and inferior
cerebral veins.
The deep cerebral veins, which are responsible for
draining deep white matter and gray matter structures
surrounding the lateral ventricles, third ventricle, and
interpeduncular cistern, are distinguished from the
superficial veins both by position and by drainage
polarity: while the superficial veins drain centrifugally
toward the lateral parts of the sinus system, the deep
veins drain centripetally, converging at midline as the
great cerebral vein of Galen.[9] These veins have several
named vessels among their number, including the
internal cerebral veins, the basal veins of Rosenthal,
and the great cerebral vein of Galen just mentioned.
The regionally named choroid veins, septal veins, and
thalamostriate veins join to form the internal cerebral
veins. The choroid veins receive blood from the
hippocampus, fornix, and corpus callosum. The septal
veins receive blood from the septum pellucidum and
corpus callosum. The thalamostriate veins receive blood
from the longitudinal caudate veins. The two internal
cerebral veins then run beneath the splenium of the corpus callosum until joining in this region to form the
great cerebral vein of Galen. The basal veins of Rosenthal
are formed by the union of the anterior cerebral veins,
deep middle cerebral veins (deep Sylvian vein), and
striate veins. These veins then travel posteriorly around
the cerebral peduncle to drain into the great cerebral vein
of Galen, which, in turn, curves posteriorly to drain into
the straight sinus.
Both the cerebral veins and sinuses have neither valves
nor a tunica muscularis layer, and the cerebral veins
are linked by numerous anastomoses. These qualities
give the venous system a substantial compensatory
capacity in the event of a major occlusion. The result
of this compensatory capacity is that CVT is an
uncommon cause of cerebral infarction relative to
arterial disease: it is responsible for only 0.5%–1% of
strokes.[90] Still, it is an important consideration both
because of its potential for morbidity and its effect
on the younger population (age <50 years). Based on
a study of 624 patients, oral contraceptives (54.3%),
hereditary prothrombotic conditions (e.g., antithrombin
III deficiency, protein C and S deficiencies) (34.1%),
pregnancy (21%), parameningeal infections (12.3%),
cancer (7.4%), and antiphospholipid antibodies (5.9%)
account for the majority of the risk factors of CVT.[91] The
use of oral contraception contributes to the predominance
of females affected by the disease. Amoozegar et al. found
that third-generation oral contraceptives (desogestrel-,
gestodene-, and norgestimate-containing drugs) have
the greatest capacity to induce CVT.[92,93] Furthermore,
the combination of oral contraceptive use with a
prothrombotic condition dramatically increases the risk
of CVT.[93,94] The main cerebral venous sinuses affected
by CVT are the superior sagittal sinus (72%) and the
transverse sinuses (70%).[95] The current treatment of
choice includes intravenous heparin,[95,96] thrombolysis,[97]
and oral anticoagulation.[46,47,95]
Conclusion
In this review of the cerebral circulatory system and
cerebrovascular disease, we sought to recapitulate the
complex cerebral circulation. In doing so, we attempted
to interweave several of the more salient pathological
consequences of disruptions in this system. This involved
discussing some of the classical stroke syndromes
along with the arterial anatomy, a discussion of BBB
components that may produce edema when disturbed
along with our presentation of microcirculatory
anatomy, and a discussion of the compensatory capacity
possessed by the venous anatomy against central venous
thrombosis.
With the anatomical context thus established, we will
proceed, in Part II of our series,[64] with an introduction
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Chandra, et al.: Cerebral circulation: Anatomy54 Brain Circulation ‑ Volume 3, Issue 2, April‑June 2017to the major categories of cerebrovascular disease
mechanisms: those that are intrinsic to the vessel, those
that are extrinsic, cerebral hypoperfusion, and cerebral
hemorrhage. By combining this information with the
anatomical context established above, we hope to supply
the physiological background essential to a working
understanding of the vascular pathology of the brain.
In Part III of our review series,[17] we will seek to enrich
this understanding through a detailed presentation of its
most common and most (rightfully) reviled instantiation:
stroke.
Financial support and sponsorship
This work was partially supported by the American Heart
Association Grant-in-Aid (14GRNT20460246) (YD),
Merit Review Award (I01RX-001964-01) from the
US Department of Veterans Affairs Rehabilitation
R&D Service (YD), the National Natural Science
Foundation of China (81501141) (XG), and Beijing NOVA
program (xx2016061) (XG).
Conflicts of interest
There are no conflicts of interest.
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