Virchow-Robin Spaces
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A perivascular space, also known as a Virchow–Robin space, is a fluid-filled space surrounding certain
blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...
s in several organs, including the brain, potentially having an
immunological Immunology is a branch of biology and medicine that covers the study of immune systems in all organisms. Immunology charts, measures, and contextualizes the physiological functioning of the immune system in states of both health and disease ...
function, but more broadly a dispersive role for neural and blood-derived messengers. The brain
pia mater Pia mater ( or ),Entry "pia mater"
in
subarachnoid space. In the brain, ''perivascular cuffs'' are regions of leukocyte aggregation in the perivascular spaces, usually found in patients with
viral encephalitis Viral encephalitis is inflammation of the brain parenchyma, called encephalitis, by a virus. The different forms of viral encephalitis are called viral encephalitides. It is the most common type of encephalitis and often occurs with viral meningiti ...
. Perivascular spaces vary in dimension according to the type of blood vessel. In the brain where most capillaries have an imperceptible perivascular space, select structures of the brain, such as the
circumventricular organs Circumventricular organs (CVOs) (wiktionary:circum-, circum-: around ; ventricular: of Ventricular system, ventricle) are structures in the brain characterized by their extensive and highly vascular permeability, permeable capillary, capillarie ...
, are notable for having large perivascular spaces surrounding highly
permeable Permeability, permeable, and semipermeable may refer to: Chemistry *Drug permeability *Semipermeable membrane, a membrane which will allow certain molecules or ions to pass through it by diffusion *Vascular permeability, the movement of fluids a ...
capillaries, as observed by
microscopy Microscopy is the technical field of using microscopes to view subjects too small to be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of microscopy: optical mic ...
. The
median eminence The median eminence is generally defined as the portion of the ventral hypothalamus from which the portal vessels arise. The median eminence is a small swelling on the tuber cinereum, posterior to and on top of the pituitary stalk; it lies in th ...
, a brain structure at the base of the
hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
, contains capillaries with wide perivascular spaces. In humans, perivascular spaces surround arteries and veins can usually be seen as areas of
dilatation Dilation (or dilatation) may refer to: Physiology or medicine * Cervical dilation, the widening of the cervix in childbirth, miscarriage etc. * Coronary dilation, or coronary reflex * Dilation and curettage, the opening of the cervix and surgi ...
on MRI images. While many normal brains will show a few dilated spaces, an increase in these spaces may correlate with the incidence of several
neurodegenerative A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...
diseases, making the spaces a topic of research.


Structure

Perivascular spaces are gaps containing
interstitial fluid In cell biology, extracellular fluid (ECF) denotes all body fluid outside the Cell (biology), cells of any multicellular organism. Body water, Total body water in healthy adults is about 50–60% (range 45 to 75%) of total body weight; women ...
that span between
blood vessels Blood vessels are the tubular structures of a circulatory system that transport blood throughout many animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the tissues of a body. They also take waste an ...
and their host organ, such as the brain, which they penetrate and serve as extravascular channels through which solutes can pass. Like the blood vessels around which they form, perivascular spaces are found in both the brain subarachnoid space and the subpial space. Perivascular spaces surrounding
arteries An artery () is a blood vessel in humans and most other animals that takes oxygenated blood away from the heart in the systemic circulation to one or more parts of the body. Exceptions that carry deoxygenated blood are the pulmonary arteries in ...
in the
cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...
and the
basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...
are separated from the subpial space by one or two layers of leptomeninges, respectively, as well as the
pia mater Pia mater ( or ),Entry "pia mater"
in
veins Veins () are blood vessels in the circulatory system of humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are those of the pulmonary and fetal c ...
. Use of the
scanning electron microscope A scanning electron microscope (SEM) is a type of electron microscope that produces images of a sample by scanning the surface with a focused beam of electrons. The electrons interact with atoms in the sample, producing various signals that ...
has determined that the spaces surrounding blood vessels in the subarachnoid space are not continuous with the subarachnoid space because of the presence of pia mater cells joined by
desmosomes A desmosome (; "binding body"), also known as a macula adherens (plural: maculae adherentes) (Latin for ''adhering spot''), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like ad ...
. Perivascular spaces, especially around
fenestra A fenestra (fenestration; : fenestrae or fenestrations) is any small opening or pore, commonly used as a term in the biology, biological sciences. It is the Latin word for "window", and is used in various fields to describe a pore in an anatomy, ...
ted capillaries, are found in many organs, such as the
thymus The thymus (: thymuses or thymi) is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. The thymus ...
,
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
,
kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
s,
spleen The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in reg ...
,
bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
s, and
pineal gland The pineal gland (also known as the pineal body or epiphysis cerebri) is a small endocrine gland in the brain of most vertebrates. It produces melatonin, a serotonin-derived hormone, which modulates sleep, sleep patterns following the diurnal c ...
. Particularly within the brain circumventricular organs –
subfornical organ The subfornical organ (SFO) is one of the circumventricular organs of the brain. Its name comes from its location on the ventral surface of the fornix near the interventricular foramina (foramina of Monro), which interconnect the lateral ventric ...
,
area postrema The area postrema, a paired structure in the medulla oblongata of the brainstem, is a circumventricular organ having permeable capillaries and sensory neurons that enable its role to detect circulating chemical messengers in the blood and tra ...
, and median eminence – large perivascular spaces are present around fenestrated capillaries, indicating that the spaces serve a dispersive role for brain- or
bloodborne is a 2015 action role-playing game developed by FromSoftware and published by Sony Computer Entertainment for the PlayStation 4. The game follows a Hunter through the decrepit Gothic, Victorian-era–inspired city of Yharnam, whose inhabita ...
messengers. Perivascular spaces may be enlarged to a diameter of five millimeters in healthy humans and do not imply disease. When enlarged, they can disrupt the function of the brain regions into which they project. Dilation can occur on one or both sides of the brain. Dilated perivascular spaces are categorized into three types: * Type 1 are located on the
lenticulostriate arteries Central arteries (or perforating or ganglionic arteries) of the brain are numerous small arteries branching from the Circle of Willis, and adjacent arteries that often enter the substance of the brain through the anterior and posterior perforated ...
projecting into the
basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...
* Type 2 are located in the cortex following the path of the medullary arteries * Type 3 are located in the
midbrain The midbrain or mesencephalon is the uppermost portion of the brainstem connecting the diencephalon and cerebrum with the pons. It consists of the cerebral peduncles, tegmentum, and tectum. It is functionally associated with vision, hearing, mo ...
Perivascular spaces are most commonly located in the
basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...
and
white matter White matter refers to areas of the central nervous system that are mainly made up of myelinated axons, also called Nerve tract, tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distr ...
of the
cerebrum The cerebrum (: cerebra), telencephalon or endbrain is the largest part of the brain, containing the cerebral cortex (of the two cerebral hemispheres) as well as several subcortical structures, including the hippocampus, basal ganglia, and olfac ...
, and along the
optic tract In neuroanatomy, the optic tract () is a part of the visual system in the brain. It is a continuation of the optic nerve that relays information from the optic chiasm to the ipsilateral lateral geniculate nucleus (LGN), pretectal nuclei, and su ...
. The ideal method used to visualize perivascular spaces is T2-weighted MRI. The MR images of other
neurological Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...
disorder Disorder may refer to randomness, a lack of intelligible pattern, or: Healthcare * Disorder (medicine), a functional abnormality or disturbance * Mental disorder or psychological disorder, a psychological pattern associated with distress or disab ...
s can be similar to those of the dilated spaces. These disorders are: * cystic neoplasms * lacunar infarctions * cystic periventricular leukomalacia *
cryptococcosis Cryptococcosis is a potentially fatal fungal infection of mainly the lungs, presenting as a pneumonia, and in the brain, where it appears as a meningitis. Coughing, difficulty breathing, chest pain and fever are seen when the lungs are infect ...
*
multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...
*
mucopolysaccharidoses Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down molecules called glycosaminoglycans (GAGs). These long chains of sugar carbohydrates occur within the cel ...
*
neurocysticercosis Neurocysticercosis (NCC) is a Parasitic disease, parasitic infection of the central nervous system, nervous system caused by the larvae of the tapeworm ''Taenia solium,'' also known as the "pork tapeworm". The disease is primarily transmitted ...
*
arachnoid cyst Arachnoid cysts are cerebrospinal fluid covered by arachnoidal cells and collagen that may develop between the surface of the brain and the cranial base or on the arachnoid membrane, one of the three meningeal layers that cover the brain and th ...
s * neuroepithelial cysts Perivascular spaces are distinguished on an MRI by several key features. The spaces appear as distinct round or oval entities with a signal intensity visually equivalent to that of
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...
in the subarachnoid space. In addition, a perivascular space has no mass effect and is located along the blood vessel around which it forms.


Function

One of the most basic roles of the perivascular space is the regulation of fluid movement in the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...
and its drainage. The spaces ultimately drain fluid from neuronal cell bodies to the
cervical lymph nodes Cervical lymph nodes are lymph nodes found in the neck. Of the 800 lymph nodes in the human body, 300 are in the neck. Cervical lymph nodes are subject to a number of different pathological conditions including tumours, infection and inflamma ...
. In particular, the "tide hypothesis" suggests that the cardiac contraction creates and maintains pressure waves to modulate the flow to and from the subarachnoid space and the perivascular space. By acting as a sort of sponge, they are essential for signal transmission and the maintenance of
extracellular fluid In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 50–60% (range 45 to 75%) of total body weight; women and the obese typically ha ...
. Another function is as an integral part of the
blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...
(BBB). While the BBB is often described as the tight junctions between the endothelial cells, this is an oversimplification that neglects the intricate role that perivascular spaces take in separating the venous blood from the parenchyma of the brain. Often, cell debris and foreign particles, which are impermeable to the BBB will get through the endothelial cells, only to be
phagocytosed Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is c ...
in the perivascular spaces. This holds true for many T and
B cell B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...
s, as well as
monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also ...
s, giving this small fluid filled space an important
immunological Immunology is a branch of biology and medicine that covers the study of immune systems in all organisms. Immunology charts, measures, and contextualizes the physiological functioning of the immune system in states of both health and disease ...
role. Perivascular spaces also play an important role in immunoregulation; they not only contain
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