11

Lesson   6

 

Spinal cord

 Structure of the white and gray matter

Brain

Meninges of the brain

 

 

The adult spinal cord measures approximately 45 cm (18 in.) in length and has a maximum width of roughly 14 mm (0.55 in.). The posterior (dorsal) surface of the spinal cord bears a shallow longitudinal groove, the posterior median sulcus. The anterior median fissure is a deeper groove along the anterior (ventral) surface.

The amount of gray matter is greatest in segments of the spinal cord that deal with the sensory and motor control of the limbs. These areas are expanded, forming the enlargements of the spinal cord. The cervical enlargement supplies nerves to the shoulder girdles and upper limbs; the lumbar enlargement provides innervation to structures of the pelvis and lower limbs. Inferior to the lumbar enlargement, the spinal cord becomes tapered and conical; this region is the conus medullaris. The filum terminale ("terminal thread"), a slender strand of fibrous tissue, extends from the inferior tip of the conus medullaris. It continues along the length of the vertebral canal as far as the second sacral vertebra. There it provides longitudinal support to the spinal cord as a component of the coccygeal ligament.

The amount of gray matter is greatest in segments of the spinal cord that deal with the sensory and motor control of the limbs. These areas are expanded, forming the enlargements of the spinal cord. The cervical enlargement supplies nerves to the shoulder girdles and upper limbs; the lumbar enlargement provides innervation to structures of the pelvis and lower limbs. Inferior to the lumbar enlargement, the spinal cord becomes tapered and conical; this region is the conus medullaris. The filum terminale ("terminal thread"), a slender strand of fibrous tissue, extends from the inferior tip of the conus medullaris. It continues along the length of the vertebral canal as far as the second sacral vertebra. There it provides longitudinal support to the spinal cord as a component of the coccygeal ligament.

 

The amount of gray matter is greatest in segments of the spinal cord that deal with the sensory and motor control of the limbs. These areas are expanded, forming the enlargements of the spinal cord. The cervical enlargement supplies nerves to the shoulder girdles and upper limbs; the lumbar enlargement provides innervation to structures of the pelvis and lower limbs. Inferior to the lumbar enlargement, the spinal cord becomes tapered and conical; this region is the conus medullaris. The filum terminale ("terminal thread"), a slender strand of fibrous tissue, extends from the inferior tip of the conus medullaris. It continues along the length of the vertebral canal as far as the second sacral vertebra. There it provides longitudinal support to the spinal cord as a component of the coccygeal ligament.

Figure 13-1 provides a series of sectional views that demonstrate the variations in the relative mass of gray and white matter in the cervical, thoracic, lumbar, and sacral regions of the spinal cord. The entire spinal cord can be divided into 31 segments on the basis of the origins of the spinal nerves. Each segment is identified by a letter and number designation, as used in the identification of individual vertebrae. For example, C₃, the segment in the uppermost section of Figure 13-1, is the third cervical segment.

Every spinal segment is associated with a pair of dorsal root ganglia (Figure 13-1) that contains the cell bodies of sensory neurons. The dorsal roots, which contain the axons of these neurons, bring sensory information into the spinal cord. A pair of ventral roots contains the axons of motor neurons that extend into the periphery to control somatic and visceral effectors. On either side, the dorsal and ventral roots of each segment pass between the vertebral canal and the periphery at the intervertebral foramen between successive vertebrae. The dorsal root ganglion lies between the pedicles of the adjacent vertebrae. (You may wish to review the description of vertebral anatomy in Chapter 7, Figure 7-18)

Distal to each dorsal root ganglion, the sensory and motor roots are bound together into a single spinal nerve. Spinal nerves are classified as mixed nerves because they contain both afferent (sensory) and efferent (motor) fibers. There are 31 pairs of spinal nerves, each identified by its association with adjacent vertebrae. For example, we may speak of "cervical spinal nerves" or even "cervical nerves" when we make a general reference to spinal nerves of the neck. When we indicate specific spinal nerves, it is customary to give them a regional number, as indicated in Figure 13-1. Each spinal nerve caudal to the first thoracic vertebra takes its name from the vertebra immediately preceding it. Thus, spinal nerve T₁ emerges immediately caudal to vertebra T₁, spinal nerve T₂ follows vertebra T₂, and so forth.

The arrangement differs in the cervical region because the first pair of spinal nerves, C₁, passes between the skull and the first cervical vertebra. For this reason, each cervical nerve takes its name from the vertebra immediately following it. In other words, cervical nerve C₂ precedes vertebra C₂, and the same system is used for the rest of the cervical series. The transition from one numbering system to another occurs between the last cervical and first thoracic vertebrae. Because the spinal nerve lying between them has been designated C₈, there are only seven cervical vertebrae but eight cervical nerves.

The spinal cord continues to enlarge and elongate until an individual is approximately 4 years old. Up to that time, enlargement of the spinal cord keeps pace with the growth of the vertebral column. Throughout this period, the ventral and dorsal roots are very short, and they enter the intervertebral foramina immediately adjacent to their spinal segment. After age 4, the vertebral column continues to elongate, but the spinal cord does not. This vertebral growth carries the dorsal roots and spinal nerves farther and farther from their original positions relative to the spinal cord. As a result, the dorsal and ventral roots gradually elongate, and the correspondence between spinal segment and the vertebral segment is lost. For example, in the adult the sacral segments of the spinal cord are at the level of vertebrae L₁-L₂.

Because the adult spinal cord extends only to the level of the first or second lumbar vertebra, the dorsal and ventral roots of spinal segments L₂ to S₅ extend caudally, past the inferior tip of the conus medullaris. When seen in gross dissection, the filum terminale and the long ventral and dorsal roots resemble a horse's tail. As a result, early anatomists called the complex the cauda equina (cauda, tail + equus, horse).

SPINAL CORD (MEDULLA)

The spinal cord occupies the superior two-thirds of the vertebral canal (Fig. 18.1, Fig. 43.1). It is continuous cranially with the medulla oblongata, and narrows caudally to the conus medullaris, from whose apex a connective tissue filament, the filum terminale, descends to the dorsum of the first coccygeal vertebral segment. The cord extends from the upper border of the atlas to the junction between the first and second lumbar vertebrae: its average length in European males is 45 cm, its weight approximately 30 g. (For dimensional data consult Barson & Sands 1977.)

During development, the vertebral column elongates more rapidly than the spinal cord, so that there is an increasing discrepancy between the anatomical level of spinal cord segments and their corresponding vertebrae. At stage 23, the vertebral column and spinal cord are the same length, and the cord ends at the last coccygeal vertebra: this arrangement continues until the third fetal month. At birth, the spinal cord terminates at the lower border of the second lumbar vertebra, and may sometimes reach the third lumbar vertebra. In the adult, the spinal cord is said to terminate at the level of the disc between the first and second lumbar vertebral bodies, which lies a little above the level of the elbow joint when the arm is by the side, and also lies approximately in the transpyloric plane (p. 1054). However, there is considerable variation in the level at which the spinal cord ends. It may end below this level in as many as 40% of subjects, or opposite the body of either the first or second lumbar vertebra: very occasionally it ends as high as the caudal third of twelfth thoracic or as low as the disc between the second and third lumbar vertebrae. Its position rises slightly in vertebral flexion, and there is some correlation with the length of the trunk, especially in females. The spinal cord varies in transverse width, gradually tapering craniocaudally, except at the levels of the enlargements. It is not cylindrical, being wider transversely at all levels, especially in the cervical segments.

 

Fig. 43.1  A, Brain and spinal cord with attached spinal nerve roots and dorsal root ganglia, photographed from the dorsal aspect. Note the fusiform cervical and lumbar enlargements of the cord, and the changing obliquity of the spinal nerve roots as the cord is descended. The cauda equina is undisturbed on the right but has been spread out on the left to show its individual components. B–D, Formation of typical spinal nerve, ventral aspect. B, Cervical level; C, Thoracic level; D, Lumbar level. E, Lower end of spinal cord, filum terminale and cauda equina exposed from behind. The dura mater and the arachnoid have been opened and spread out. F, Spinal cord segment showing mode of formation of a typical spinal nerve and the gross relationships of the grey and white matter. (B–D, From Sobotta 2006.) (Dissection by MCE Hutchinson, GKT School of Medicine; photograph by Kevin Fitzpatrick on behalf of GKT School of Medicine, London.)

The cervical enlargement is the source of the large spinal nerves that supply the upper limbs. It extends from the third cervical to the second thoracic segments, its maximum circumference (approximately 38 mm) is in the sixth cervical segment. (A spinal cord segment provides the attachment of the rootlets of a pair of spinal nerves.) The lumbar enlargement is the source of the large spinal nerves that supply the lower limbs, and extends from the first lumbar to the third sacral segments, the equivalent vertebral levels being the ninth to twelfth thoracic vertebrae. Its greatest circumference (approximately 35 mm) is near the lower part of the body of the twelfth thoracic vertebra, below which it rapidly dwindles into the conus medullaris.

Fissures and sulci extend along most of the external surface. An anterior median fissure and a posterior median sulcus and septum almost completely separate the cord into right and left halves, but they are joined by a commissural band of nervous tissue which contains a central canal.

The anterior median fissure extends along the whole ventral surface with an average depth of 3 mm, although it is deeper at caudal levels. It contains a reticulum of pia mater. Dorsal to it is the anterior white commissure. Perforating branches of the spinal vessels pass from the fissure to the commissure to supply the central spinal region. The posterior median sulcus is shallower, and from it a posterior median septum penetrates more than halfway into the cord, almost to the central canal. The septum varies in anteroposterior extent from 4 to 6 mm, and diminishes caudally as the canal becomes more dorsally placed and the cord contracts.

A posterolateral sulcus exists from 1.5 to 2.5 mm lateral to each side of the posterior median sulcus. Dorsal roots (strictly rootlets) of spinal nerves enter the cord along the sulcus. The white substance between the posterior median and posterolateral sulcus on each side is the posterior funiculus. In cervical and upper thoracic segments a longitudinal posterointermediate sulcus marks a septum dividing each posterior funiculus into two large tracts: the fasciculus gracilis (medial) and fasciculus cuneatus (lateral). Between the posterolateral sulcus and anterior median fissure is the anterolateral funiculus. This is subdivided into anterior and lateral funiculi by ventral spinal rootlets which pass through its substance to issue from the surface of the cord. The anterior funiculus is medial to, and includes, the emerging ventral rootlets, whilst the lateral funiculus lies between the roots and the posterolateral sulcus. In upper cervical segments, nerve rootlets emerge through each lateral funiculus to form the spinal accessory nerve which ascends in the vertebral canal lateral to the spinal cord and enters the posterior cranial fossa via the foramen magnum (Fig. 28.11).

The filum terminale, a filament of connective tissue approximately 20 cm long, descends from the apex of the conus medullaris. Its upper 15 cm, the filum terminale internum, is continued within extensions of the dural and arachnoid meninges and reaches the caudal border of the second sacral vertebra. Its final 5 cm, the filum terminale externum, fuses with the investing dura mater, and then descends to the dorsum of the first coccygeal vertebral segment. The filum is continuous above with the spinal pia mater. A few strands of nerve fibres which probably represent roots of rudimentary second and third coccygeal spinal nerves adhere to its upper part. The central canal is continued into the filum for 5–6 mm. A capacious part of the subarachnoid space surrounds the filum terminale internum, and is the site of election for access to the CSF (lumbar puncture).

DORSAL AND VENTRAL ROOTS

The paired dorsal and ventral roots of the spinal nerves are continuous with the spinal cord (Fig. 43.1F; see also p. 754). They cross the subarachnoid space and traverse the dura mater separately, uniting in or close to their intervertebral foramina to form the (mixed) spinal nerves. Since the spinal cord is shorter than the vertebral column, the more caudal spinal roots descend for varying distances around and beyond the cord to reach their corresponding foramina. In so doing they form a divergent sheaf of spinal nerve roots, the cauda equina, which is gathered round the filum terminale in the spinal theca, mostly distal to the apex of the cord.

Ventral spinal roots contain efferent somatic and, at some levels, preganglionic sympathetic, axons which extend from neuronal cell bodies in the ventral horns and intermediolateral columns respectively. There are also afferent nerve fibres in these roots. The rootlets comprising each ventral root emerge from the anterolateral sulcus in groups over an elongated vertical elliptical area (Fig. 43.1F). Dorsal spinal roots bear ovoid swellings, the spinal ganglia, one on each root proximal to its junction with a corresponding ventral root in an intervertebral foramen. Each root fans out into six to eight rootlets before entering the cord in a vertical row in the posterolateral sulcus. Dorsal roots are usually said to contain only afferent axons (both somatic and visceral) which are the central processes of unipolar neurones in the spinal root ganglia, but they may also contain a small number (3%) of efferent fibres and autonomic vasodilator fibres.

Each ganglionic neurone has a single short stem which divides into a medial (central) branch which enters the spinal cord via a dorsal root, and a lateral (peripheral) branch which passes peripherally to a sensory end organ. The central branch is an axon while the peripheral one is an elongated dendrite (but when traversing a peripheral nerve is, in general structural terms, indistinguishable from an axon). The region of spinal cord associated with the emergence of a pair of nerves is a spinal segment, but there is no actual surface indication of segmentation. Moreover, the deep neural sources or destinations of radicular fibres may lie far beyond the confines of the ‘segment’ so defined.

Spinal Meninges

The vertebral column and its surrounding ligaments, tendons, and muscles isolate the spinal cord from the external environment. The delicate neural tissues must also be defended against damaging contacts with the surrounding bony walls of the vertebral canal. A series of specialized membranes, the spinal meninges (meninx, membrane), provide the necessary physical stability and shock absorption. Blood vessels branching within these layers also deliver oxygen and nutrients to the spinal cord.

The relationships among the spinal meninges are shown in Figure 13-2a. There are three meningeal layers: (1) the dura mater, (2) the arachnoid, and (3) the pia mater. At the foramen magnum of the skull, the spinal meninges are continuous with the cranial meninges that surround the brain. (We shall discuss the cranial meninges, which have the same three layers, in Chapter 14.)

Bacterial or viral infection can cause meningitis, or inflammation of the meningeal membranes. Meningitis is dangerous because it can disrupt the normal circulatory and cerebrospinal fluid supplies, damaging or killing neurons and glial cells in the affected areas. Although an initial diagnosis may specify the meninges of the spinal cord (spinal meningitis) or brain (cerebral meningitis), in later stages the entire meningeal system is usually affected.

The Dura Mater

The tough, fibrous dura mater (dura, hard + mater, mother) forms the outermost covering of the spinal cord (Figure 13-2a). The dense collagen fibers of the dura mater are oriented along the longitudinal axis of the cord. Between the dura mater and the walls of the vertebral canal lies the epidural space, which contains loose connective tissue, blood vessels, and a protective padding of adipose tissue (Figure 13-2b).

The dura mater does not have extensive, firm connections to the surrounding vertebrae. Longitudinal stability is provided by localized attachment sites at either end of the vertebral canal. Cranially, the outer layer of the dura mater fuses with the periosteum of the occipital bone around the margins of the foramen magnum. Within the sacral canal, the dura mater tapers from a sheath to a dense cord of collagen fibers that blend with components of the filum terminale to form the coccygeal ligament.

The coccygeal ligament continues along the sacral canal, ultimately blending into the periosteum of the coccyx. Lateral support for the dura mater is provided by loose connective tissue and adipose tissue within the epidural space. In addition, the dura mater extends between adjacent vertebrae at each intervertebral foramen, fusing with the connective tissues that surround the spinal nerves.

Injecting an anesthetic into the epidural space will affect only the spinal nerves in the immediate area of the injection. The result is a temporary sensory and motor paralysis known as an epidural block. Epidural blocks in the lower lumbar or sacral regions may be used to control pain during childbirth.

 

The Arachnoid

In most anatomical and histological preparations, a narrow subdural space separates the dura mater from deeper meningeal layers. It is likely, however, that in life no such space exists and that the inner surface of the dura mater is in contact with the outer surface of the arachnoid (arachne, spider) (Figure 13-2b). The inner surface of the dura mater and the outer surface of the arachnoid are covered by simple squamous epithelia. The arachnoid includes the epithelium and the subarachnoid space, which contains the arachnoid trabeculae, a delicate network of collagen and elastic fibers maintained by modified fibroblasts. The subarachnoid space is filled with cerebrospinal fluid, which acts as a shock absorber as well as a diffusion medium for dissolved gases, nutrients, chemical messengers, and waste products.

The arachnoid membrane extends caudally as far as the filum terminale, and the dorsal and ventral roots of the cauda equina travel within the fluid-filled subarachnoid space. In adults, the withdrawal of cerebrospinal fluid, a procedure known as a spinal tap, involves the insertion of a needle into the subarachnoid space in the lower lumbar region (Figure 13-3a). This placement avoids the possibility of damage to the spinal cord. Spinal taps are performed when CNS infection is suspected or to diagnose severe back pain, headaches, disc problems, and some types of strokes.

The Pia Mater

The subarachnoid space bridges the gap between the arachnoid epithelium and the innermost meningeal layer, the pia mater (pia, delicate + mater, mother). The meshwork of elastic and collagen fibers of the pia mater are interwoven with those of the subarachnoid space. The blood vessels servicing the spinal cord are found here. Unlike more superficial meninges, the pia mater is firmly bound to the underlying neural tissue (Figure 13-2b).

Along the length of the spinal cord, paired denticulate ligaments extend from the pia mater through the arachnoid to the dura mater. Denticulate ligaments, which originate along either side of the spinal cord (Figure 13-2b), prevent lateral (side-to-side) movement. The dural connections at the foramen magnum and the coccygeal ligament prevent longitudinal (superior/inferior) movement.

The spinal meninges accompany the dorsal and ventral roots as they pass through the intervertebral foramina. As indicated in the sectional view of Figure 13-2b, the meningeal membranes are continuous with the connective tissues that surround the spinal nerves and their peripheral branches.

CONCEPT CHECK QUESTIONS

1.     Damage to which root of a spinal nerve would interfere with motor function?

2.     Where is the cerebrospinal fluid that surrounds the spinal cord located?

Sectional Anatomy of the Spinal Cord

To understand the functional organization of the spinal cord, you must become familiar with its sectional organization. The anterior median fissure and the posterior median sulcus mark the division between left and right sides of the spinal cord. The superficial white matter contains large numbers of myelinated and unmyelinated axons. The gray matter, dominated by the cell bodies of neurons, glial cells, and unmyelinated axons, surrounds the narrow central canal and forms an H or butterfly shape. The projections of gray matter toward the outer surface of the spinal cord are called horns. Figure 13-4 presents a typical section through the spinal cord.

Organization of Gray Matter

The cell bodies of neurons in the gray matter of the spinal cord are organized into functional groups called nuclei. Sensory nuclei receive and relay sensory information from peripheral receptors. Motor nuclei issue motor commands to peripheral effectors. Although sensory and motor nuclei appear rather small in transverse section, they may extend for a considerable distance along the length of the spinal cord.

A frontal section along the length of the central canal of the spinal cord will separate the sensory (posterior, or dorsal) nuclei from the motor (anterior, or ventral) nuclei. The posterior gray horns contain somatic and visceral sensory nuclei, whereas the anterior gray horns contain somatic motor nuclei. The lateral gray horns, located only in the thoracic and lumbar segments, contain visceral motor nuclei. The gray commissures (commissura, a joining together) posterior to and anterior to the central canal contain axons that cross from one side of the cord to the other before they reach a destination within the gray matter.

Figure shows the relationship between the function of a particular nucleus (sensory or motor) and its relative position within the gray matter of the spinal cord. The nuclei within each gray horn are also organized. For example, the anterior gray horns of the cervical enlargement contain nuclei whose motor neurons control the muscles of the upper limbs. On each side of the spinal cord, in medial to lateral sequence, are motor nuclei that control (1) muscles that position the shoulder girdle, (2) muscles that position the arm, (3) muscles that move the forearm and hand, and (4) muscles that move the hand and fingers. Within each of these regions, the motor neurons that control flexor muscles are grouped separately from those that control extensor muscles. Because the spinal cord is so highly organized, we can predict the muscles that will be affected by damage to a specific area of gray matter.

Organization of White Matter

The white matter on each side of the spinal cord can be divided into three regions called columns, or funiculi (Figure 13-4a). The posterior white columns lie between the posterior gray horns and the posterior median sulcus. The anterior white columns lie between the anterior gray horns and the anterior median fissure. The anterior white columns are interconnected by the anterior white commissure. The white matter between the anterior and posterior columns on each side makes up the lateral white column.

Each column contains tracts whose axons share functional and structural characteristics. A tract, or fasciculus (bundle), is a bundle of axons in the CNS that are relatively uniform with respect to diameter, myelination, and conduction speed. All the axons within a tract relay the same type of information (sensory or motor) in the same direction. Short tracts carry sensory or motor signals between segments of the spinal cord, and longer tracts connect the spinal cord with the brain.

INTERNAL ORGANIZATION

In transverse section, the spinal cord is incompletely divided into symmetrical halves by a dorsal (posterior) median septum and a ventral (anterior) median sulcus (Fig. 18.1). It consists of an outer layer of white matter and an inner core of grey matter; their relative sizes and configuration vary according to level. The amount of grey matter reflects the number of neurones present; it is proportionately largest in the cervical and lumbar enlargements, which contain the neurones that innervate the limbs. The absolute amount of white matter is greatest at cervical levels, and decreases progressively at lower levels, because descending tracts shed fibres as they descend and ascending tracts accumulate fibres as they ascend.

Fig. 18.1  Transverse sections through the spinal cord at representative levels. Approximately ×5. (Figure enhanced by B Crossman.)

A diminutive central canal, lined by columnar, ciliated epithelium (ependyma) and containing cerebrospinal fluid (CSF), extends the whole length of the spinal cord lying in the centre of the spinal grey matter. Rostrally, the central canal extends into the caudal half of the medulla oblongata and then opens into the fourth ventricle.

SPINAL GREY MATTER

In three dimensions, the spinal grey matter is shaped like a fluted column (Fig. 43.1F). In transverse section the column is often described as being ‘butterfly-shaped’ or resembling the letter ‘H’ (Fig. 18.1). It consists of four linked cellular masses, the right and left dorsal and ventral horns, that project dorsolaterally and ventrolaterally towards the surface respectively. The grey matter that immediately surrounds the central canal and unites the two sides constitutes the dorsal and ventral grey commissures. The dorsal horn is the site of termination of the primary afferent fibres that enter the cord via the dorsal roots of spinal nerves. The tip of the dorsal horn is separated from the dorsolateral surface of the cord by a thin fasciculus or tract (of Lissauer) in which primary afferent fibres ascend and descend for a short distance before terminating in the subjacent grey matter. The ventral horn contains efferent neurones whose axons leave the spinal cord in ventral nerve roots. A small intermediate, or lateral, horn is present at thoracic and upper lumbar levels; it contains the cell bodies of preganglionic sympathetic neurones.

Spinal grey matter (Fig. 18.2) is a complex mixture of neuronal cell bodies, their processes and synaptic connections, neuroglia and blood vessels. Neurones in the grey matter are multipolar. They vary in size and features such as the length and the arrangement of their axons and dendrites. Neurones may be intrasegmental, i.e. contained within a single segment, or intersegmental, i.e. their ramifications spread through several segments.

Fig. 18.2  Transverse section of spinal cord at a midlumbar level. The larger motor neurones in the ventral grey column are visibly grouped. Stained with cresyl fast violet.

Neuronal cell groups of the spinal cord

Viewed from the perspective of its longitudinal columnar organization, the grey matter of the spinal cord consists of a series of discontinuous cell groupings associated with their corresponding segmentally arranged spinal nerves. At any particular cross-sectional level these cell groupings are often considered to correspond approximately with one or more of ten cell layers, known as Rexed's laminae. These laminae are defined on the basis of neuronal size, shape, cytological features and density and are numbered in a dorsoventral sequence.

Laminae I–IV correspond to the dorsal part of the dorsal horn, and are the main site of termination of cutaneous primary afferent terminals and their collaterals. Many complex polysynaptic reflex paths (ipsilateral, contralateral, intrasegmental and intersegmental) start from this region, as also do many long ascending tract fibres which pass to higher levels. Lamina I (lamina marginalis) is a very thin layer with an ill-defined boundary at the dorsolateral tip of the dorsal horn. It has a reticular appearance, reflecting its content of intermingling bundles of coarse and fine nerve fibres. It contains small, intermediate and large neuronal somata, many of which are fusiform in shape. The much larger lamina II consists of densely packed small neurones, responsible for its dark appearance in Nissl-stained sections. With myelin stains, lamina II is characteristically distinguished from adjacent laminae by the almost total lack of myelinated fibres. Lamina II corresponds to the substantia gelatinosa. Lamina III consists of somata which are mostly larger, more variable and less closely packed than those in lamina II. It also contains many myelinated fibres. Some workers consider that the substantia gelatinosa contains part or all of lamina III as well as lamina II. The ill-defined nucleus proprius of the dorsal horn corresponds to some of the cell constituents of laminae III and IV. Lamina IV is a thick, loosely packed, heterogeneous zone permeated by fibres. Its neuronal somata vary considerably in size and shape, from small and round, through intermediate and triangular, to very large and stellate.

Laminae V and VI lie at the base of the dorsal horn. They receive most of the terminals of proprioceptive primary afferents, profuse corticospinal projections from the motor and sensory cortex and input from subcortical levels, suggesting their involvement in the regulation of movement. Lamina V is a thick layer, divisible into a lateral third and medial two-thirds. Both have a mixed cell population but the former contains many prominent well-staining somata interlaced by numerous bundles of transverse, dorsoventral and longitudinal fibres. Lamina VI is most prominent in the limb enlargements. It has a densely staining medial third of small, densely packed neurones and a lateral two-thirds containing larger, more loosely packed, triangular or stellate somata.

Laminae VII–IX show a variety of forms in the limb enlargements. Lamina VII includes much of the intermediate (lateral) horn. It contains prominent neurones of Clarke's column (nucleus dorsalis, nucleus thoracis, thoracic nucleus) and intermediomedial and intermediolateral cell groupings (Fig. 18.3). The lateral part of lamina VII has extensive ascending and descending connections with the midbrain and cerebellum (via the spinocerebellar, spinotectal, spinoreticular, tectospinal, reticulospinal and rubrospinal tracts) and is thus involved in the regulation of posture and movement. Its medial part has numerous propriospinal reflex connections with the adjacent grey matter and segments concerned both with movement and autonomic functions. Lamina VIII spans the base of the thoracic ventral horn but is restricted to its medial aspect in limb enlargements. Its neurones display a heterogeneous mixture of sizes and shapes from small to moderately large. Lamina VIII is a mass of propriospinal interneurones. It receives terminals from the adjacent laminae, many commissural fibres from the contralateral lamina VIII, and descending connections from the interstitiospinal, reticulospinal and vestibulospinal tracts and the medial longitudinal fasciculus. The axons from these interneurones influence α motor neurone activity bilaterally, perhaps directly but more probably by excitation of small γ motor neurones supplying efferent fibres to muscle spindles. Lamina IX is a complex array of cells consisting of α and γ motor neurones and many interneurones. The large α motor neurones supply motor end-plates of extrafusal muscle fibres in striated muscle. Recording techniques have demonstrated tonic and phasic α motor neurones. The former have a lower rate of firing and lower conduction velocity and tend to innervate type S muscle units. The latter have higher conduction velocity and tend to supply fast twitch (type FR, FF) muscle units. The smaller γ motor neurones give rise to small-diameter efferent axons (fusimotor fibres), which innervate the intrafusal muscle fibres in muscle spindles. There are several functionally distinct types of γ motor neurone. The ‘static’ and ‘dynamic’ responses of muscle spindles have separate controls mediated by static and dynamic fusimotor fibres, which are distributed variously to nuclear chain and nuclear bag fibres.

Lamina X surrounds the central canal and consists of the dorsal and ventral grey commissures.

Dorsal horn

The dorsal horn is a major zone of termination of primary afferent fibres, which enter the spinal cord through the dorsal roots of spinal nerves. Dorsal root fibres contain numerous molecules, which are either known, or suspected, to fulfil a neurotransmitter or neuromodulator role. These include glutamic acid, substance P, calcitonin gene-related peptide (CGRP), bombesin, vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), somatostatin, dynorphin and angiotensin II. Dorsal root afferents carry exteroceptive, proprioceptive and interoceptive information. Laminae I–IV are the main cutaneous receptive areas; lamina V receives fine afferents from the skin, muscle and viscera; lamina VI receives proprioceptive and some cutaneous afferents. Most, if not all, primary afferent fibres divide into ascending and descending branches on entering the cord. These then travel for variable distances in the tract of Lissauer, near the surface of the cord, and send collaterals into the subjacent grey matter. The formation, topography and division of dorsal spinal roots have all been confirmed in man.

The lamina marginalis is a thin lamina of neurones at the dorsolateral tip of the dorsal horn, deep to the tract of Lissauer. Beneath it lies the substantia gelatinosa (laminae II and III), which is present at all levels, and consists mostly of small neurones, together with some larger neurones. The substantia gelatinosa receives afferents via the dorsal roots, and its neurones give rise to fibres that form the contralateral spinothalamic tract. The large propriospinal neurones of the nucleus proprius lie ventral to the substantia gelatinosa; they link segments for the mediation of intraspinal coordination (Fig. 18.3).

Fig. 18.3  The groups of nerve cells in the grey columns of the spinal cord. The relative positions of these columnar groups and their extent through spinal segments are indicated. (Modified with the permission of Simon & Schuster from Correlative Anatomy of the Nervous System by E. Crosby, T. Humphrey, E. Lauer. Copyright © 1962 Macmillan Publishing Company.)

 

Clarke's column lies at the base of the dorsal horn. At most levels, it is near the dorsal white funiculus and may project into it. In the human spinal cord, it can usually be identified from the eighth cervical to the third or fourth lumbar segments. Neurones of Clarke's column vary in size, but most are large, especially in the lower thoracic and lumbar segments. Some send axons into the dorsal spinocerebellar tracts and others are interneurones.

Lateral horn

The lateral horn is a small lateral projection of grey matter located between the dorsal and ventral horns. It is present from the eighth cervical or first thoracic segment to the second or third lumbar segment. It contains the cell bodies of preganglionic sympathetic neurones. These develop in the embryonic cord dorsolateral to the central canal and migrate laterally, forming intermediomedial and intermediolateral cell columns. Their axons travel via ventral spinal roots and white rami communicantes to the sympathetic trunk. A similar cell group is found in the second to fourth sacral segments, but unlike the thoracolumbar lateral cell column, it does not form a visible lateral projection. It is the source of the sacral outflow of parasympathetic preganglionic nerve fibres.

Ventral horn

Neurones in the ventral horn vary in size. The largest cell bodies, which may exceed 25 μm in diameter, are those of α motor neurones, the axons of which emerge in ventral roots to innervate extrafusal fibres in striated skeletal muscles. Large numbers of smaller neurones, 15–25 μm in diameter, are also present. Some of these are γ motor neurones, which innervate intrafusal fibres of muscle spindles, and the rest are interneurones. Motor neurones utilize acetylcholine as their neurotransmitter.

Considered longitudinally, ventral horn neurones are arranged in elongated groups, and form a number of separate columns, which extend through several segments. These are seen most easily in transverse sections. The ventral horn may be divided into medial, central and lateral cell columns, which all exhibit subdivision at certain levels, usually into dorsal and ventral parts (Fig. 18.3). The medial group extends throughout the cord, but may be absent in the fifth lumbar and first sacral segments. In the thoracic and the upper four lumbar segments, it is subdivided into ventromedial and dorsomedial groups. In segments cranial and caudal to this region, the medial group has only a ventromedial moiety, except in the first cervical segment, where only the dorsomedial group exists.

The central group of cells is the least extensive, and is found only in some cervical and lumbosacral segments. The centrally situated phrenic nucleus, containing the motor neurones that innervate the diaphragm, lies in the third to seventh cervical segments. An irregular accessory group of neurones in the upper five or six cervical segments at the ventral border of the ventral horn give rise to axons that are thought to enter the spinal accessory nerve (Fig. 18.3).

The lateral group of cells in the ventral horn is subdivided into ventral, dorsal and retrodorsal groups, largely confined to the spinal segments which innervate the limbs. The nucleus of Onuf, which is thought to innervate the perineal striated muscles, is a ventrolateral group of cells in the first and second sacral segments.

The motor neurones of the ventral horn are somatotopically organized. The basic arrangement is that medial cell groups innervate the axial musculature, and lateral cell groups innervate the limbs. The basic building block of the somatic motor neuronal populations is represented by a longitudinally disposed group of neurones, which innervate a given muscle, and in which the α and γ motor neurones are intermixed. The various groups innervating different muscles are aggregated into two major longitudinal columns, medial and lateral. In transverse section these form the medial and lateral cell groups in the ventral horn (Fig. 18.4).

Fig. 18.4  The approximate location of motor cell groups at C8 segmental level of the spinal cord.

The medial longitudinal motor column extends throughout the length of the spinal cord. Its neurones innervate epaxial and hypaxial muscle groups. Basically, epaxial muscles include the erector spinae group (which extend the head and vertebral column), while hypaxial muscles include prevertebral muscles of the neck, intercostal and anterior abdominal wall muscles (which flex the neck and the trunk). The epaxial muscles are innervated by branches of the dorsal primary rami of the spinal nerves, and the hypaxial muscles by branches of the ventral primary rami. In the medial column, motor neurones supplying epaxial muscles are sited ventral to those supplying hypaxial muscles.

The lateral longitudinal motor column is found only in the enlargements of the spinal cord. The motor neurones in this column in the cervical and lumbar enlargements innervate muscles of the upper and lower limbs, respectively. In the cervical enlargement, motor neurones which supply muscles intrinsic to the upper limb are situated dorsally in the ventral grey column, and those innervating the most distal (hand) muscles are sited further dorsally. Motor neurones of the girdle muscles lie in the ventrolateral part of the ventral horn. There is a further somatotopic organization in that the proximal muscles of the limb are supplied from motor cell groups located more rostrally in the enlargement than those supplying the distal muscles. For example, motor neurones innervating intrinsic muscles of the hand are sited in segments C8 and T1, while motor neurones of shoulder muscles are in segments C5 and 6. A similar overall arrangement of motor neurones innervating lower limb muscles applies in the lumbosacral cord (Fig. 18.5).

Fig. 18.5  The segmental arrangement of motor neurones innervating muscles of the lower limb.

The main afferent connections to motor neurones are: direct monosynaptic connections from proprioceptive dorsal root afferents in the same or nearby segments; connections from axonal collaterals of dorsal horn and other interneurones; direct monosynaptic connections from the vestibulospinal and corticospinal tracts.

Spinal reflexes

The intrinsic connections of the spinal cord and brain stem subserve a number of reflexes by which the functions of peripheral structures are modulated in response to afferent information in a relatively automatic or autonomous fashion. The fundamental components of such reflex ‘arcs’ are, thus, an afferent and an efferent neurone. However, in all but the simplest of reflexes, interneurones intervene between the afferent and efferent components, conferring increased versatility and complexity on reflex responses. Reflexes, by their very nature, are relatively fixed and stereotyped in form. Nevertheless, they are strongly influenced and modulated by descending connections. In the case of spinal reflexes these descending controls come from both the brain stem and the cerebral cortex. Pathology of descending supraspinal pathways commonly causes abnormalities of spinal reflex activity, which are routinely tested for in neurological examination. During development, descending control mechanisms suppress what may be regarded as ‘primitive’ spinal reflex responses, such as the extensor plantar reflex and the grasp reflex. When the higher control mechanisms become damaged, these reflexes are released and reappear as a sign of CNS pathology (e.g. the Babinski reflex).

Stretch reflex

The stretch reflex is the mechanism by which stretch applied to a muscle elicits its reflex contraction. It is essential for the maintenance of both muscle tone and an upright stance (via the innervation of the postural muscles of the neck, back and lower limbs). Anatomically it is the simplest of reflexes, since it is mediated solely by an afferent and an efferent neurone. The afferent component arises from stretch receptors associated with intrafusal muscle fibres located within muscle spindles. The primary or annulospiral endings of these receptive cells give rise to primary afferent fibres which enter the spinal cord, where they make excitatory synaptic contact directly onto α motor neurones innervating the same muscle (Fig. 18.6). The α motor neurones of antagonistic muscles are simultaneously inhibited via collateral connections to inhibitory interneurones.

Fig. 18.6  The stretch reflex. (By permission from Crossman AR, Neary D 2000 Neuroanatomy, 2nd edn. Edinburgh: Churchill Livingstone.)

Gamma reflex

As well as α motor neurones innervating extrafusal muscle fibres, muscles also receive γ motor neurones, which innervate intrafusal muscle fibres. Activation of γ motor neurones increases the sensitivity of the intrafusal fibres to stretch (Fig. 18.7). Therefore, changes in γ activity have a profound effect upon the stretch reflex and upon muscle tone. Like α motor neurones, γ motor neurones are under the influence of descending pathways from the brain stem and cerebral cortex. Changes in the activity of the stretch reflex and of muscle tone are commonly found in disorders of the CNS as well as the PNS.

Fig. 18.7  The gamma reflex. (By permission from Crossman AR, Neary D 2000 Neuroanatomy, 2nd edn. Edinburgh: Churchill Livingstone.)

Flexor reflex

Painful stimulation of the limbs leads to flexion withdrawal, that is mediated by a polysynaptic reflex (Fig. 18.8) in which interneurones link the afferent and efferent neurones. Thus, activation of nociceptive primary afferents indirectly causes activation of limb flexor motor neurones. Collateralization of fibres to nearby spinal segments mediates flexion of a limb at several joints, depending on the intensity of the stimulus. Decussating connections to the contralateral side of the cord activate α motor neurones innervating corresponding extensor muscles, which produces the so-called crossed extensor reflex. In principle, virtually any cutaneous stimulus has the potential to induce a flexor reflex, but, other than in the case of noxious stimuli, this response is normally inhibited by descending pathways. When descending influences are lost, even harmless cutaneous stimulation can elicit flexion of the limbs. The Babinski (extensor plantar) reflex, which is generally regarded as pathognomonic of damage to the corticospinal tract, is part of a flexion withdrawal of the lower limb in response to stimulation of the sole of the foot.

Fig. 18.8  The flexor reflex and crossed extensor reflex. (By permission from Crossman AR, Neary D 2000 Neuroanatomy, 2nd edn. Edinburgh: Churchill Livingstone.)

 

 

 Ascending tracts carry sensory information toward the brain, and descending tracts convey motor commands into the spinal cord.

CONCEPT CHECK QUESTIONS

1.     A person with polio has lost the use of his leg muscles. In what area of the spinal cord would you expect the virally infected motor neurons to be in this individual?

2.     What portion of the spinal cord would be affected by a disease that damages myelin sheaths?

Brain

Meninges of the brain

Our perceptions of the world around us depend on thousands of interactions among neurons within the central nervous system. We seldom realize how complex these processes are unless they go wrong in some way. For example, a child with dyslexia has a condition characterized by difficulties with the recognition and use of words. Although the cause of dyslexia remains a mystery, there is general agreement that it results from problems with the integration and processing of visual or auditory information. There is much that we still do not understand about such activities, which ultimately create our consciousness and our unique personalities. This chapter introduces the brain regions involved in our conscious and subconscious thought processes and considers complex neural functions, such as memory and learning.

 

The adult human brain contains almost 98 percent of the body's neural tissue. A "typical" brain weighs 1.4 kg (3 lb) and has a volume of 1200 cc (71 in.³). There is considerable individual variation in brain size, and the brains of males average about 10 percent larger than those of females, owing to differences in average body size. No correlation exists between brain size and intelligence. Individuals with the smallest brains (750 cc) and the largest brains (2100 cc) are functionally normal.

Embryology of the Brain

To introduce the organization of the adult brain, we will consider its embryological origins. The development of the brain is detailed in the Embryology Summary on pages 454-455. The CNS begins as a hollow neural tube with a fluid-filled internal cavity called the neurocoel. In the cephalic portion of the neural tube, three areas enlarge rapidly through expansion of the neurocoel. This enlargement creates three prominent divisions called primary brain vesicles. The primary brain vesicles are named for their relative positions: the prosencephalon (proso, forward + enkephalos, brain), or "forebrain"; the mesencephalon (mesos, middle), or "midbrain"; and the rhombencephalon, or "hindbrain."

The fate of the three primary divisions of the brain is summarized in Table 14-1. The prosencephalon and rhombencephalon are subdivided further, forming secondary brain vesicles. The prosencephalon forms the telencephalon (telos, end) and the diencephalon (dia, through). The tel-encephalon will ultimately form the cerebrum of the adult brain. The mesencephalon thickens, and the neurocoel becomes a relatively narrow passageway comparable to the central canal of the spinal cord. The portion of the rhombencephalon adjacent to the mesencephalon forms the metencephalon (meta, after). The dorsal portion of the metencephalon will become the cerebellum, and the ventral portion will develop into the pons. The portion of the rhombencephalon closer to the spinal cord forms the myelencephalon (myelon, spinal cord), which will become the medulla oblongata.

A Preview of Major Regions and Landmarks

The adult brain is dominated in size by the cerebrum:

• Cerebrum.
  Viewed from the anterior and superior surfaces (Figure 14-1a,b), the cerebrum of the adult brain can be divided into large, paired cerebral hemispheres. Conscious thoughts, sensations, intellect, memory, and complex movements originate in the cerebrum. The surfaces of the cerebral hemispheres and cerebellum are highly folded and covered by neural cortex (cortex, rind or bark), a superficial layer of gray matter. The term cerebral cortex refers to the neural cortex of the cerebral hemispheres, as opposed to the cerebellar cortex of the cerebellar hemispheres.

Second in size to the cerebrum is the cerebellum:

• Cerebellum.
  The hemispheres of the cerebellum are partially hidden by the cerebral hemispheres (Figure 14-1a,bc,d). The cerebellum adjusts ongoing movements on the basis of comparisons between arriving sensations and sensations experienced previously, allowing you to perform the same movements.

The other major regions of the brain can best be examined after the cerebral hemispheres have been removed (Figure 14-2).

• Diencephalon.
  The walls of the diencephalon are composed of the left and right thalamus. Each thalamus contains relay and processing centers for sensory information. A narrow stalk, the infundibulum, connects the hypothalamus (hypo-, below), or floor of the diencephalon, to the pituitary gland, a component of the endocrine system. The hypothalamus contains centers involved with emotions, autonomic function, and hormone production. As we shall see in Chapter 18, it is the primary link between the nervous and endocrine systems.

The diencephalon is a structural and functional link between the cerebral hemispheres and the components of the brain stem. The brain stem includes the mesencephalon, pons, and medulla oblongata. (Some sources consider the brain stem to include the diencephalon. We will use the more restrictive definition here). It contains a variety of important processing centers and nuclei that relay information headed to or from the cerebrum or cerebellum:

• Mesencephalon.
  Sensory nuclei in the mesencephalon, or midbrain, process visual and auditory information and control reflexes triggered by these stimuli. For example, your immediate, reflexive responses to a loud, unexpected noise (eye movements and head turning) are directed by nuclei in the midbrain. This region also contains centers involved with the maintenance of consciousness.

• Pons.
  The term pons is Latin for "bridge"; the pons of the brain connects the cerebellum to the brain stem. In addition to tracts and relay centers, the pons also contains nuclei involved with somatic and visceral motor control.

• Medulla oblongata.
  The spinal cord connects to the brain at the medulla oblongata. Near the pons, the roof of the medulla oblongata is thin and membranous. The caudal portion of the medulla oblongata resembles the spinal cord in that it has a narrow central canal. The medulla oblongata relays sensory information to the thalamus and to centers in other portions of the brain stem. The medulla oblongata also contains major centers concerned with the regulation of autonomic function, such as heart rate, blood pressure, and digestion.

The boundaries and general functions of the diencephalon and brain stem are listed in Figure 14-2.

CONCEPT CHECK QUESTIONS

1.     What are the three primary brain vesicles, and what does each contribute to the structure of the adult brain?

2.     In response to a loud noise, your head automatically turns toward the source of the sound. What part of the brain directs this response?

Ventricles of the Brain

During development, the neurocoel within the cerebral hemispheres, diencephalon, metencephalon, and medulla oblongata expands to form chambers called ventricles. The ventricles are lined by cells of the ependyma.

Each cerebral hemisphere contains an enlarged ventricle. A thin medial partition, the septum pellucidum, separates this pair of lateral ventricles. There is no direct connection between the two lateral ventricles, but each communicates with the ventricle of the diencephalon through an interventricular foramen (foramen of Monro) (Figure 14-3). Because there are two lateral ventricles (first and second), the one in the diencephalon is called the third ventricle.

The mesencephalon has a slender canal known as the mesencephalic aqueduct (aqueduct of Sylvius or cerebral aqueduct). This passageway connects the third ventricle with the fourth ventricle. The superior portion of the fourth ventricle lies between the posterior surface of the pons and the anterior surface of the cerebellum. The fourth ventricle extends into the superior portion of the medulla oblongata (Figure 14-3a). This ventricle then narrows and becomes continuous with the central canal of the spinal cord (Figure 14-3a).

The ventricles are filled with cerebrospinal fluid. There is a continuous circulation of cerebrospinalfluid (CSF) from the ventricles and central canal into the subarachnoid space of the meninges that surround the CNS. The CSF passes between the interior and exterior of the CNS through foramina in the roof of the fourth ventricle.

PROTECTION AND SUPPORT OF THE BRAIN

The delicate tissues of the brain are protected from mechanical forces by (1) the bones of the cranium,(2) the cranial meninges, and (3) cerebrospinal fluid. In addition, the neural tissue of the brain is biochemically isolated from the general circulation by the blood-brain barrier.

The Cranial Meninges

The layers that make up the cranial meninges—the dura mater, arachnoid, and pia mater—are continuous with those of the spinal cord. However, the cranial meninges have distinctive anatomical and functional characteristics.

• The dura mater consists of outer and inner fibrous layers. The outer layer is fused to the periosteum of the cranial bones. As a result, there is no epidural space comparable to that surrounding the spinal cord. The outer, or endosteal, and inner, or meningeal, layers are separated by a slender gap that contains tissue fluids and blood vessels, including large venous channels known as dural sinuses. The veins of the brain open into these sinuses, which deliver the venous blood to the internal jugular veins of the neck.

• The arachnoid consists of the arachnoid membrane and the cells and fibers of the subarachnoid space. The arachnoid membrane covers the brain, providing a smooth surface that does not follow the brain's underlying folds. The arachnoid membrane, an epithelial layer, is in contact with the inner epithelial layer of the dura mater. The subarachnoid space extends between the arachnoid membrane and the pia mater.

• The pia mater sticks to the surface of the brain, anchored by the processes of astrocytes. It extends into every fold and curve and accompanies the branches of cerebral blood vessels as they penetrate the surface of the brain to reach internal structures.

Functions of the Cranial Meninges

The brain is cradled within the cranium. There is an obvious correspondence between the shape of the brain and that of the cranial cavity (Figure 14-4a). The massive cranial bones provide mechanical protection, but they also pose a threat. The brain is like a person driving a car. If the car hits a tree, the car protects the driver from contact with the tree, but serious injury will occur unless a seat belt or airbag protects the driver from contact with the car.

Cranial trauma is a head injury resulting from impact with another object. There are roughly 8 million cases of cranial trauma each year in the United States, but only 1 case in 8 results in serious brain damage. The percentage is relatively low because the cranial meninges provide effective protection for the brain. Tough, fibrous dural folds act like safety belts that hold the brain in position. The cerebrospinal fluid contained in the subarachnoid space acts like an airbag that cushions sudden jolts and shocks.

Cranial Trauma

Dural Folds
In several locations, the inner layer of the dura mater extends into the cranial cavity, forming a sheet that dips inward and then returns. These dural folds provide additional stabilization and support to the brain. Dural sinuses may be found between the two layers of a dural fold. The three largest dural folds are called the falx cerebri, the tentorium cerebelli, and the falx cerebelli (Figure 14-4b):

1.     The falx cerebri (falx, curving or sickle-shaped) is a fold of dura mater that projects between the cerebral hemispheres in the longitudinal fissure. Its inferior portions attach anteriorly to the crista galli and posteriorly to the internal occipital crest. Two large venous sinuses, the superior sagittal sinus and the inferior sagittal sinus, travel within this dural fold. The posterior margin of the falx cerebri intersects the tentorium cerebelli.

2.     The tentorium cerebelli (tentorium, a covering) separates and protects the cerebellar hemispheres from those of the cerebrum. It extends across the cranium at right angles to the falx cerebri. The transverse sinus lies within the tentorium cerebelli.

3.     The falx cerebelli divides the two cerebellar hemispheres along the midsagittal line inferior to the tentorium cerebelli.

Cerebrospinal Fluid

Cerebrospinal fluid (CSF) completely surrounds and bathes the exposed surfaces of the CNS. The CSF has several important functions, including the following:

• Cushioning delicate neural structures.

• Supporting the brain.
  In essence, the brain is suspended inside the cranium and floats in the cerebrospinal fluid. A human brain weighs about 1400 g in air but only about 50 g when supported by the cerebrospinal fluid.

• Transporting nutrients, chemical messengers, and waste products.
  Except at the choroid plexus, where CSF is produced, the ependymal lining is freely permeable, and the CSF is in constant chemical communication with the interstitial fluid of the CNS.

Because free exchange occurs between the interstitial fluid and CSF, changes in CNS function may produce changes in the composition of the CSF. As we noted in Chapter 13, a spinal tap can provide useful clinical information concerning CNS injury, infection, or disease.

The Formation of CSF

The choroid plexus (choroid, vascular coat; plexus, network) consists of a combination of specialized ependymal cells and permeable capillaries for the production of cerebrospinal fluid. Two extensive folds of the choroid plexus originate in the roof of the third ventricle and extend through the interventricular foramina. These folds cover the floors of the lateral ventricles (Figure 14-5a). In the lower brain stem, a region of the choroid plexus in the roof of the fourth ventricle projects between the cerebellum and pons.

Specialized ependymal cells, interconnected by tight junctions, surround the capillaries of the choroid plexus. The ependymal cells secrete CSF into the ventricles; they also remove waste products from the CSF and adjust its composition over time. The differences in composition between CSF and blood plasma (blood with the cellular elements removed) are quite pronounced. For example, the blood contains high concentrations of soluble proteins, but the CSF does not. There are also differences in the concentrations of individual ions and in the levels of amino acids, lipids, and waste products.

Circulation of CSF

The choroid plexus produces CSF at a rate of about 500 ml/day. The total volume of CSF at any given moment is approximately 150 ml; thus, the entire volume of CSF is replaced roughly every 8 hours. Despite this rapid turnover, the composition of CSF is closely regulated, and the rate of removal normally keeps pace with the rate of production.

The CSF circulates from the choroid plexus through the ventricles and the central canal of the spinal cord (Figure 14-5a). As the CSF circulates, there is unrestricted diffusion between it and the interstitial fluid of the CNS between and across the ependymal cells. The CSF reaches the subarachnoid space through two lateral apertures and a single median aperture in the roof of the fourth ventricle. Cerebrospinal fluid then flows through the subarachnoid space surrounding the brain, spinal cord, and cauda equina.

Along the axis of the superior sagittal sinus, fingerlike extensions of the arachnoid membrane, called the arachnoid villi, penetrate the dura mater. In adults, clusters of villi form large arachnoid granulations (Figure 14-5b). Cerebrospinal fluid is absorbed into the venous circulation at the arachnoid granulations. If the normal circulation or reabsorption of CSF is interrupted, a variety of clinical problems may appear. For example, a problem with the reabsorption of CSF in infancy is responsible for symptoms of hydrocephalus, or "water on the brain." Infants with this condition have enormously expanded skulls due to the presence of an abnormally large volume of CSF.

Hydrocephalus

In an adult, failure of reabsorption or blockage of CSF circulation can cause distortion and damage to the brain.

The Blood Supply to the Brain

As we noted in Chapter 12, neurons have a high demand for energy, and they have neither energy reserves, in the form of carbohydrates or lipids, nor oxygen reserves, in the form of myoglobin. Your brain, with billions of neurons, is an extremely active organ with a continuous demand for nutrients and oxygen. These demands are met by an extensive circulatory supply. Arterial blood reaches the brain through the internal carotid arteries and the vertebral arteries. Most of the venous blood from the brain leaves the cranium in the internal jugular veins, which drain the dural sinuses. A head injury that damages cerebral blood vessels may cause bleeding into dura mater, either near the dural epithelium or between the outer layer of the dura mater and the bones of the skull. These are serious conditions because the blood entering these spaces compresses and distorts the relatively soft tissues of the brain.

Edipural snd Subdural Hemorrhages

Cerebrovascular diseases are circulatory disorders that interfere with the normal circulatory supply to the brain. The particular distribution of the vessel involved will determine the symptoms, and the degree of oxygen or nutrient starvation will determine their severity. A stroke, or cerebrovascular accident (CVA) , occurs when the blood supply to a portion of the brain is shut off. Affected neurons begin to die in a matter of minutes.

The Blood-Brain Barrier

Neural tissue in the CNS is isolated from the general circulation by the blood-brain barrier. This barrier exists because the endothelial cells that line the capillaries of the CNS are extensively interconnected by tight junctions. These junctions prevent the diffusion of materials between adjacent endothelial cells. In general, only lipid-soluble compounds (including carbon dioxide, oxygen, ammonia, lipids, such as steroids or prostaglandins, and small alcohols) can diffuse across the lipid bilayer membranes of endothelial cells into the interstitial fluid of the brain and spinal cord. Water and ions must pass through channels in the inner and outer cell membranes. Larger water-soluble compounds can cross the capillary walls only through active or passive transport. The restricted permeability characteristics of the endothelial lining of brain capillaries are in some way dependent on chemicals secreted by astrocytes. We described these cells, which are in close contact with CNS capillaries, in Chapter 12. The outer surfaces of the endothelial cells are covered by the processes of astrocytes. Because the astrocytes release chemicals that control the permeabilities of the endothelium, these cells play a key supporting role in the blood-brain barrier. If the astrocytes are damaged or stop stimulating the endothelial cells, the blood-brain barrier disappears.

The choroid plexus lies outside the neural tissue of the brain, and there are no astrocytes in contact with the endothelial cells. As a result, capillaries there are highly permeable. Substances do not have free access to the CNS, however, because a blood-CSF barrier is created by specialized ependymal cells. These cells, interconnected by tight junctions, surround the capillaries of the choroid plexus.

Transport across the blood-brain and blood-CSF barriers is selective and directional. Even the passage of small ions, such as sodium, hydrogen, potassium, or chloride, is controlled. As a result, the pH and concentrations of sodium, potassium, calcium, and magnesium ions in the blood and CSF are different. Some organic compounds are readily transported, and others cross only in minute amounts. Neurons have a constant need for glucose. This need must be met regardless of the relative concentrations in the blood and interstitial fluid. Even when circulating glucose levels are low, endothelial cells continue to transport glucose from the blood to the interstitial fluid of the brain. In contrast, only trace amounts of circulating norepinephrine, epinephrine, dopamine, or serotonin pass into the interstitial fluid or CSF of the brain. This limitation is important because these compounds are neurotransmitters, and their entry from the circulation (where concentrations can be relatively high) could result in the uncontrolled stimulation of neurons throughout the brain.

The blood-brain barrier remains intact throughout the CNS, with four noteworthy exceptions:

1.     In portions of the hypothalamus, the capillary endothelium is extremely permeable. This permeability exposes hypothalamic nuclei to circulating hormones and permits the diffusion of hypothalamic hormones into the circulation.

2.     Capillaries in the posterior pituitary gland are highly permeable. At this site, the hormones ADH and oxytocin, produced by hypothalamic neurons, are released into the circulation.

3.     Capillaries in the pineal gland are also very permeable. The pineal gland, an endocrine structure, is located in the posterior, superior surface of the diencephalon. The capillary permeability allows pineal secretions into the general circulation.

4.     Capillaries at the choroid plexus are extremely permeable. Although the capillary characteristics of the blood-brain barrier are lost there, the transport activities of specialized ependymal cells within the choroid plexus maintain the blood-CSF barrier.

CONCEPT CHECK QUESTIONS

1.     What would happen if an interventricular foramen became blocked?

2.     How would decreased diffusion across the arachnoid granulations affect the volume of cerebrospinal fluid in the ventricles?

3.     Many water-soluble molecules found in the blood in relatively large amounts occur in small amounts or not at all in the extracellular fluid of the brain. Why?