General Properties of the BBB 1 страница

Large molecules do not pass through the BBB easily.

Low lipid (fat) soluble molecules do not penetrate into the brain. However, lipid soluble molecules, such as barbiturate drugs, rapidly cross through into the brain.

Molecules that have a high electrical charge are slowed.

Some parts of the CNS, however, are not isolated from substances carried in the blood. The barrier is ineffective or absent in the neurohypophysis, substantia nigra and locus ceruleus.

Spinal cord

The spinal cord is organized into two discrete parts. The outer part contains ascending and descending nerve fibers. These fibers are divided into longitudinal columns or funiculi. They constitute the white matter of the cord. The inner part contains cell bodies of neurons and nerve fibers. This is the gray matter of the spinal cord. Spinal gray matter is butterfly-shaped or H shaped. It extends from the ependymal cells lining the central canal to the surrounding white matter. Spinal gray matter is divided bilaterally into dorsal horn, intermediate substance, and ventral horn. At thoracolumbar levels, intermediate substance features a lateral horn. Intermediate substance lacks precise boundaries; in general, it is around the central canal and between dorsal and ventral horns.

Figure 3. Cross section of the human spinal cord. VH, ventral horns; DH, dorsal horns; GC, gray commissure; V, ventral fissure

Spinal neurons within the gray matter are either efferent neurons (axons enter ventral roots), projection neurons (axons join white matter tracts), or interneurons (axons remain within gray matter). The gray matter "horns" are actually profiles of gray columns. Columns of neuron cell bodies, when transected, appear as clusters of neuron cell body profiles within gray matter. The cell body clusters are called nuclei. So, functionally related groups of nerve cell bodies in the gray matter are called nuclei. Functionally related bundles of axons in the white matter are called tracts. Some nuclei (columns of cell bodies) are present throughout the spinal cord; other nuclei have more restricted segmental distributions. The dorsal horn surface is capped by a marginal nucleus (lamina I) which is thin and not distinct in transverse sections. A population of small neurons forms a very distinctive substantia gelatinosa (lamina II). The remainder of the dorsal horn may be considered nucleus proprius. The nucleus thoracicus, located medially in the base of the dorsal horn, is present in thoracolumbar segments; axons from the nucleus form the dorsal spinocerebellar tract (Note: nucleus thoracicus projection neurons are large but sparse and not evident in some sections). In the intermediate substance, one nucleus is found only in thoracic and cranial lumbar segments of the spinal cord. The intermediolateral nucleus, which forms a lateral horn, is composed of sympathetic preganglionic neurons.
The ventral horn contains somatic efferent motor neurons. Medial motor nuclei innervate muscles of the trunk and are found in all spinal segments. Lateral collections of motor neurons, which innervate limb muscle, are seen in segments of the cervical and lumbosacral enlargements. Motor nuclei are somatotopically arranged. Much of the spinal gray matter is outside of recognizable nuclei. An alternative of method of categorizing gray matter involves defining spinal laminae, as opposed to nuclei. Laminae offer the advantage of including all regions of gray matter. The disadvantage of laminae is that, unlike nuclei, laminar boundaries are not evident in normal sections.

Sensory ganglia

Sensory ganglia house cell bodies of sensory neurons. Sensory ganglia of die spinal nerves are called dorsal root ganglia. Sensory neurons in the dorsal root ganglia are pseudounipolar. They have a single process that divides into a peripheral segment that brings information from the periphery to the cell body and a central segment that carries information from the cell body into the gray matter of the spinal cord. Because the sensory neuron conducts impulses to the CNS, it is called an afferent neuron. The ganglions are surrounded by a connective tissue capsule composed of collagen.

EYE

The eyes are complex sensory organs that provide us with the sense of sight. The wall of the eye consists of three concentric layers or coats.

-Corneoscleral coat, the outer or fibrous layer that includes the sclera and the cornea.

-Uvea, the middle layer or vascular coat that includes the choroid and the stroma of the ciliary body and iris.

-Retina, the inner layer that includes an outer pigment epithelium, the inner neural retina, and the epithelium of the ciliary body and iris.

Figure 4. Schematic diagram illustrating the internal structures of the human eye

Chambers of the eye

The layers of the eye and the lens serve as boundaries for three chambers within the eye.

The chambers of the eye are:

-anterior chamber, occupying the space between the cornea and the iris

-posterior chamber, occupying the space between the posterior surface of the iris and the anterior surface of the lens

-vitreous space occupying the space between the posterior surface of the lense and the neural retina

The refractile media components of the eye

The refractile media components of the eye alter the light path to focus it on the retina.

They are

-cornea

-aqueous humor

-lens

-vitreous body (or humor)

The cornea

The corneoscleral coat consists of the transparent cornea and the white opaque sclera. The cornea covers the anterior one-sixth of the eye. The cornea is continuous with the sclera. The sclera is composed of dense fibrous connective tissue that provides attachment for the extrinsic muscles of the eye. It is continuous with the conjunctival epithelium that overlies the adjacent sclera. Numerous free nerve endings in the corneal epithelium provide it with extreme sensivity to touch.

The cornea consists of five layers: three cellular layers and two lamellae.

Figure 5. Electron micrograph of the cornea

The corneal epithelium is nonkeratinized stratified squamous epithelium.

Bowman’s membrane is a homogenous fibrillar lamina on which the corneal epithelium rests. Bowman’s membrane ends abruptly at the limbus, the junction of the cornea and sclera. Bowman’s membrane provides strength to the cornea and is a barrier to the spread of infections.

The corneal stroma constitutes 90% of the corneal thickness. It is composed of about 60 thin lamellae between which are found flattened fibroblasts. Each lamella consists of parallel bundles of collagen fibrils. The ground substance contains corneal proteoglycans, sulfated glycosaminoglycans (keratansulfate). The normal cornea contains no blood vessels or pigments.

Descement’s membrane is an unusually thick basal lamina of the corneal endothelial cells.

The corneal endothelium is a single layer of flattened cells covering the surface of the cornea that faces the anterior chamber. It provides metabolic exchange between cornea and aqueous humor.

The sclera

The sclera is an opaque layer consisting of dense connective tissue. Flat collagen bundles pass in various directions in planes to the surface of the sclera. Interspersed between the collagen bundles are fine networks of elastic fibers and a moderate amount of ground substance. Fibroblasts are scattered among these fibers. The opacity of the sclera is due primarily to the irregularity of its structure. The sclera is pierced by blood vessels, nerves, and the optic nerve.

The sclera is divided into three layers:

-episclera

-sclera proper

-lamina fusca

Limbus

The limbus is the transitional zone between cornea and sclera. It is the limbus region that contains the apparatus for the outflow of aqueous humor. In the stromal layer, endothelium-lined channels called the trabecular meshwork merge to form the canal of Schlemm, which drains fluid from the anterior chamber of the eye.

Figure 6. Schematic diagram of the structure of the eye

Iris

The iris forms a contractile diaphragm anterior to the lens surface. The iris arises from the anterior border of the ciliary body. The pupil is the central aperture of this thin disc.

The layers of the iris, from anterior to posterior, consist of

- fibroblasts and melanocytes in a discontinuous layer, marked with ridges and grooves.

-a thin avascular layer of stroma, the anterior stromal sheet or lamella

-a loose connective tissue layer that contains many small blood vessels and constitutes the main mass of the iris

-a discontinuous layer of smooth muscle that is derived from the anterior epithelial cells and is called the posterior membrane

-a double layer of pigmented epithelial cells

Two muscles, the sphincter pupillae and the dilator pupillae, form the posterior membrane. The dilator pupillae is a thin sheet of smooth muscle radially oriented near the posterior border of the iris. The sphincter pupillae is a circular band of smooth muscle located at the papillary margin. The size of the pupil is controlled by the contraction of the papillary sphincter and dilator muscles.

The function of the pigment-containing cells in the iris is to absorb light rays. The number of melanocytes in the stroma is responsible for variation in eye color.

Ciliary body

The ciliary body is a thickened anterior portion of the tunica vasculosa, located between iris and choroid. The anterior third of the ciliary body has ciliary processes. The layers of the ciliary body are similar to those of the iris, consisting of a stroma and an epithelium. The stroma is divided into two layers:

-an outer layer of smooth muscle, the ciliary muscle, that makes up the bulk of the ciliary body

-an inner vascular region that extends into the ciliary processes

The smooth muscle of the ciliary body is organized in three functional groups of fibers based on location:

-tensor portion, consisting of meridional muscle fiber

-radial portion

-circular portion

The pull of the circular and radial fibers combine to reduce the tension on the zonule, so the lens becomes more spherical in shape.

Ciliary processes are ridge-like extensions of the ciliary body from which zonulae fibers emerge and extend to the lens. The ciliary epithelium is a double layer of columnar epithelial cells which covers the ciliary body. It has three principal functions

-secretions of aqueous humor

-serving as the major component of the blood-aqueous barrier

-secretion and anchoring of the zonular fibers that form the suspensory ligament of the lens

The layer of the epithelium that has its basal lamina facing the posterior chamber is nonpigmented. The layer that has its basal lamina facing the connective tissue stroma of the ciliary body is pigmented and is directly continuous with the pigmented epithelial layer of the retina.

Choroid

The choroid is the portion of the vascular layer that lies between the sclera and the retina.

Two layers can be identified in the choroid:

-choriocapillary layer, an inner vascular layer

-Bruch’s membrane, a thin, amorphous, hyaline membrane

Retina

It consists of two basic layers:

-Neural retina or retina proper, an inner layer that contains the photoreceptors

-Retinal pigment epithelium, an outer layer that rests on and is firmly attached to the choriocapillary layer of the choroid.

Figure 7. Schematic drawing of the layers of the retina

In the neural retina, two regions or portions that differ in function are recognized:

- The nonphotosensitive region, located anterior to the ora serrata that lines the inner aspect of the ciliary body and the posterior surface of the iris.

- The photosensitive region that lines the inner surface of the eye posterior to the ora serrata except where it is pierced by the optic nerve.

The site where the optic nerve joins the retina is called the optic papilla or disc. Because the optic papilla is devoid of photoreceptors, it is a blind spot in the visual acuity. The fovea centralis is a shallow depression that is located lateral to the optic disc. It is the area of greatest visual acuity. The visual axis of the eye passes through the fovea. A yellow pigmented zone called the macula lutea surrounds the fovea.

The layers of cells and their processes constitute the neural retina.

Before identifying the ten layers of the retina, it is important to identify the types of cells found there. For convenience, neurons and supporting cells can be classified into four groups of cells:

-photoreceptors − the retinal rods and cones

-conducting neurons − bipolar and ganglion cells

-association and other neurons − horizontal, centrifugal and amacrine

-supporting cells − Müllers cells and neuroglial cells

The layers of the retina, from outside inward are defined here.

1. Pigment epithelium − the outer layer of the retina not part of the neural retina but intimately associated with it.

2. Layer of rods and cones − contains the outer and inner segments of photoreceptor cells.

3. External (outer) limiting membrane − the apical boundary of Müllers cells.

4. Outer nuclear layer − contains the cell bodies (nuclei) of retinal rods and cones.

5. Outer plexiform layer −contains the processes of retinal rods and cones and processes of the horizontal, amacrine and bipolar cells that connect to them.

6. Inner nuclear layer − contains the cell bodies (nuclei) of horizontal, amacrine, bipolar and Müllers cells.

7. Inner plexiform layer − contains the processes, amacrine, bipolar and ganglion cells that connect to each other.

8. Ganglion cell layer − contains the cell bodies (nuclei) of large multipolar ganglion cells.

9. Layer of optic nerve fibers − contains processes of ganglion cells that lead from the retina to the brain.

10. Internal (inner) limiting membrane − composed of the basal lamina of Müllers cells which separating the retina from the vitreous body.

Some of the layers are more fully described in the following sections.

The retinal pigment epithelium (RPE) is a single layer of cuboidal cells. The cells of the RPE have extensions that surround the processes of the rods and cones. Melanin granules and residual bodies are present in the cytoplasm of RPE.

The RPE serves several important functions including

-absorption of the light passing through neural retina to prevent reflection

-isolation of the retinal cells from blood borne substances

-phagocytosis and disposal of membranous discs from the rods and cones of the retinal photoreceptor cells

The rods and cones are the outer segments of photoreceptor cells whose nuclei form the outer nuclear layer of the retina. It is important to recognize that the light that reaches photoreceptors must first pass through all of the other more internal layers of the neural retina. The retina contains approximately 120 million rods and 7 million cones. Functionally the rods are more sensitive to light and are the receptors used during periods of low light intensity (at dark or during the night). The visual image provided is one composed of gray tones (a black and white picture). In contrast, the cones exist in three forms that cannot be distinguished morphologically. They are less sensitive to low light and have maximal sensivity to the red, green or blue region of the visual spectrum

Figure 8. Schematic diagram of the ultrastructure of rod and cone cells

Each rod and cone photoreceptor consists of three parts:

-outer segment

-connecting stalk

-inner segment

The outer segment of the photoreceptor is roughly cylindrical or conical in shape (hence, the descriptive name rod or cone).

The connecting stalk contains a cilium composed of 9 peripheral microtubule doublets extending from the basal body. The connecting stalk joins the inner to the outer segment.

The inner segment is divided into an outer ellipsoid and an inner myoid portion. This segment contains a prominent Golgi apparatus, rER, free polysomes, mitochondria and microtubules.

Figure 9. Transmission electron micrographs of portions of the inner and outer segment of the a rod cell(left) and a cone cell (right)

The outer segment is the site of photosensitivity, and the inner segment contains the metabolic machinery to support the activity of the photoreceptors.

1000 regularly spaced horizontal discs are seen in the outer segment. Each rode discs is a membrane-enclosed compartment within the cytoplasm. The parallel membranes of the discs are continuous at their ends. Thus, rod discs lose their continuity with the plasma membrane. Discs within the cones retain their continuity with plasma membrane. The interior of the discs of cones is continuous with the extracellular space. In rod cells, the discs contain the pigment rhodopsin. In cone cells, the discs contain the pigment iodopsin. Rhodopsin initiates the visual stimulus as it is bleached by light.

The visual pigments, rhodopsin and iodopsin are molecules that have a membrane-bound subunit called an opsin and a second component called a chromophore. The chromophore of the rods is a vitamin A derived carotenoid called retinal.

Vision is a process by which light striking the retina is converted into electrical impulses that are transmitted to the brain. The conversion of the incident light into nerve impulses is called transduction and involves two basic steps:

-step 1 is a photochemical reaction causes conformational changes in the chromophores (In rods absorbed light energy causes conformational changes in retinal, converting it to retinol.)

-step 2 causes the photoreceptors to become hyperpolarized

During the normal functioning of the photoreceptors, the membranous discs of the outer segment are shed and phagocytized by the pigment epithelial cells.

The external (outer) limiting membrane is formed by a row of zonulae adherents between the apical ends of Müller’s cells, i.e., the end that faces the pigment epithelium, with each other and with the rods and cones.

The outer nuclear layer contains the nuclei of the retinal rods and cones. The cone nuclei stain lightly and are larger and more oval than rod nuclei.

Specialized regions of retina

The fovea appears as a shallow depression located at the posterior pole of the optical axis of the eye. The central region is known as fovea centralis. Most of the layers of the retina except the layer photoreceptors are markedly reduced or absent in this region. Here, that layer composed entirely of cones and rods.

The macula lutea is the area surrounding the fovea. It is yellowish due to the presence of yellow pigment (xanthophyll). Retinal vessels are absent in this region.

Here, the retinal cells and their processes, especially the ganglion cells, are heaped up on the sides of the fovea so that light may pass unimpeded to this most sensitive area of the retina.

Crystalline lens

Figure 10. Schematic diagram of the lens

The lens is a transparent, avascular, biconvex structure. It is suspended between the edges of the ciliary body by the suspensory ligament. The lens has three principal components:

-lens capsule

-subcapsular epithelium

-lens fibers

The pull of the zonular fibers keeps the lens in a flattened condition. Release of that tension causes the lens to fatten or accommodate to bend light rays originating close to the eye so that they focus on the retina.

Vitreous humor

Vitreous humor is the transparent jelly-like substance that fills the posterior segment (vitreous space) of the eye. The main body of the vitreous is a homogenous gel containing about 99% of water, hyaluronic acid, widely dispersed collagen fibers, and other proteins and glycoproteins.

Accessory structure of the eye

The conjunctiva lines the space between the inner surface of the eyelids and the anterior surface of the eye lateral to the cornea. It consists of a stratified columnar epithelium containing numerous goblet cells and rests on a lamina propria composed of loose connective tissue.

The primary function of the eyelids is to protect the eye. Within each eyelid is a flexible support, the tarsal plate, consisting of dense fibrous and elastic tissue.

Figure 11. Schematic diagram of the eyelid

The eyelid contains three types of glands:

-Meibomian glands

-glands of Zeis

-glands of Moll

Figure 12. Schematic diagram of the eye and its accessory glands

The lacrimal gland

The lacrimal gland produces the tears that moisten the cornea and pass to the nasolacrimal duct.

Tears are produced by lacrimal and tarsal glands. Tears are sterile and contain the antibacterial enzyme lysozyme. The eye is moved within the orbit by the extraocular muscles.

Ear

The ear is a three chambered sensory structure that in the auditory system functions in the perception of sound and in the vestibular system functions in the maintenance of balance. Each of the three divisions of the ear, the external, the middle and the internal ear, is an essential part of the auditory system. The external and middle ear collect and conduct sound energy to the inner ear, where auditory sensory receptors transducer that energy into the electrical energy of nerve impulses. The sensory receptors of the vestibular system are also located in the inner ear. These receptors respond to the gravity and movement of the head.

Figure 13. Schematic illustration of the three divisions of the ear: external ear, middle ear and inner ear

External ear

The external ear is composed of an auricle and an external auditory meatus. Thin skin with hair follicles, sweat glands and sebaceous glands covers the auricle. The meatus is an air-filled tubular space that follows a slightly S-shaped course for about 25 mm to the tympanic membrane (eardrum).

The lateral part of the canal is lined by skin that contains hair follicles, sebaceous glands, and ceruminous glands.

Middle ear

The middle ear is an air-filled space that contains three small bones, the ossicles. The middle ear also contains the auditory tube (Eustachian tube).

The primary functions of the middle ear is to convert sound waves (air vibrations) arriving from the external auditory meatus into mechanical vibrations that are transmitted to the inner ear. Two openings in the medial wall of the middle ear, the vestibular (oval) window and the cochlear (round) window, are essential components in this conversion process. The tympanic membrane (eardrum) separates the external auditory canal from the middle ear. The layers of the tympanic membrane from outside to inside are

-the skin of the external auditory canal

-a core of radially and circularly arranged collagen fibers

-the epithelial lining (mucous membrane) of the inner ear

One of the auditory ossicles, the malleus, is attached to the tympanic membrane.

Figure 14. Photomicrograph of the three articulated human middle ear ossicles

The auditory ossicles (the malleus, the incus and the stapes) cross the space of the middle ear in series and connect the tympanic membrane to the oval window. These bones help to convert sound waves, i.e., vibrations in air, to mechanical vibrations in tissues and fluid-filled chambers.

The auditory (Eustachian) tube connects the middle ear to the nasopharynx. The auditory (Eustachian) tube, a narrow flattened channel lined with ciliated pseudostratified columnar epithelium. It vents the middle ear, allowing pressure in the middle ear to equilibrate with atmospheric pressure.

Inner ear

Figure 15. Photomicrograph of the human inner ear

The inner ear consists of two labyrinthine compartments, one contained within the other. The bony (osseous) labyrinth is a complex system of interconnected cavities and canals in the petrous portion of the temporal bone. The membranous labyrinth lies within the bony labyrinth and consists of a complex system of small sacs and tubules that also form continuous spaces enclosed within a wall of epithelium and connective tissue.

There are three fluid-filled spaces in the inner ear.

Endolymphatic space contained within the membranous labyrinth.

Perilymphatic space lies between the wall of the bony labyrinth and the wall of the membranous labyrinth.

Cortilymphatic space lies within the organ of Corti.

The bony labyrinth consists of three connected spaces within the temporal bone

-semicircular canals

-vestibule

-cochlea

Figure 16. Diagrams of the human inner ear bony labyrinth a, membranous inner ear labyrinth b, and the sensory regions of the inner ear c

The vestibule is the central space that contains the utricle and saccule of the membranous labyrinth which lie in an elliptical and spherical recess, respectively.

The semicircular canals extend from the vestibule posteriorly, and the cochlea extends from the vestibule anteriorly. The vestibular (oval) window into which the footplate of the stapes inserts lies in the lateral wall of the vestibule.

The semicircular canals are bony walled tubes that lie at right angles to each other in superior, posterior and horizontal planes. At the lateral end of semicircular canal close to the vestibule is dilation called an ampulla. Each inner ear has three ampullae. The three canals open into the vestibule through five orifices, with the superior and posterior semicircular canals sharing a common crus medially.

The cochlea is a conically shaped helix connected to the vestibule. The lumen of the cochlea, like that of the semicircular canals, is continuous with that of the vestibule. It connects to the vestibule on the side opposite the semicircular canals. Between its base and the apex the cochlea makes about 2,5 turns around a central bony core called the modiolus. A sensory ganglion, the spiral ganglion, lies in the modiolus (a central bony core). One opening of the canal, the cochlear (round) window is covered by the secondary tympanic membrane.

Membranous labyrinth, like bony labyrinth is divided into three subcompartments.

-membranous semicircular ducts

-utricle and saccule

-membranous cochlea (cochlea duct)

Membranous semicircular ducts lie within the bony semicircular canals and are continuous with the utricle.

The utricle and saccule are contained in recesses in the vestibule and are connected by the membranous utriculosaccular duct. The membranous cochlear duct is contained within the bony cochlea and is continuous with the saccule.

The membranous semicircular ducts, utricle and saccule are components of the vestibular system. The membranous cochlea is part of the auditory system.

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