the brain and spinal cord are composed of:
• White matter, which consists mostly of myelinated nerve fibers along with some unmyelinated fibers and neuroglial cells. the abundant myelin covering the axons gives it the white color.
• Gray matter, which consists of accumulations of neuronal cell bodies and their dendrites along with unmyelinated axons. the gray color indicates the absence of myelin.
the twisted, intertwined collection of axons, den- drites, and processes of neuroglial cells composes the neuropil. localized collections of nerve bodies in the white matter are known as nuclei. Within the brain, gray matter is located on the periphery, whereas white matter is located deeper; in the spinal cord, gray matter is located deep to the white matter. in cross section of the spinal cord, the gray matter forms the letter H, and in its center is the central canal, a small foramen lined with ependymal cells that con- tains CSF. central processes of sensory neurons ter- minate on interneuron cell bodies in the dorsal horns, the superior aspects of the vertical bars of the h. interneuron axons terminate on motoneuron cell bodies in the inferior vertical bars of the h, the ventral horns. Axons of the motoneurons exit the spinal cord by passing out the ventral roots.
MENINGES
the meninges represent the three connective tissue coverings of the brain and spinal cord identified as the outer layer, the dura mater; an intermediate arach- noid; and the innermost layer, the pia mater (Fig.
9.14).
1. Dura mater, the outermost layer of the meninges, is different in the brain than in the spinal cord. the cranial dura mater is composed of dense connective tissue consisting of two separate components:
• An outer periosteal layer closely adhered to the bony cranium, serving also as the periosteum of the inner aspect of the skull.
it is highly vascularized and contains
osteoprogenitor cells, fibroblasts, and bundles of type i collagen.
• the innermost layer of the dura, the
meningeal layer, which presents dark-staining fibroblasts possessing long processes, fine collagen fibers organized in sheets, and is vascularized by small arteries. the innermost
region of the meningeal layer, the border cell layer, consists of a thin layer of fibroblasts enveloped by an unstructured extracellular matrix lacking collagen fibers that extends into the meningeal layer.
the spinal dura mater is not represented in layers because it does not adhere to the vertebral canal as a periosteal layer. Rather, the spinal dura mater forms a complete tube surrounding the spinal cord begin- ning at the foramen magnum and ending at the second sacral segment. Along this tract, spinal nerves pierce the spinal dura, and the space between the bony vertebral canal and the dura, the epidural space, is filled with epidural fat and a venous plexus.
2. the avascular arachnoid consists of two layers:
• one is a flat sheetlike layer that lies against the dura mater.
• the second layer is formed of sparse, loosely organized modified fibroblasts (arachnoid trabecular cells) interspersed with a few fibers of collagen and some elastic fibers from trabeculae that contact the pia mater.
• the space between the flat sheet contacting the dura and the trabeculae contacting the pia is known as the subarachnoid space.
• Blood vessels course through the arachnoid as they progress from the dura on their way to the pia mater, but they are isolated from the arachnoid and from the subarachnoid space by a sheet of fibroblasts derived from the arachnoid. the subarachnoid space is a real space filled with csF, but the subdural space, located between the dura and the sheetlike layer of the arachnoid that contacts the dura, is only a potential space. specialized regions of the arachnoid, known as arachnoid villi, extend into the dural venous sinuses and translocate csF from the subarachnoid space into these dural sinuses.
3. the innermost layer of the meninges, the pia mater, is composed of flattened fibroblasts, mast cells, macrophages, and lymphocytes, and is described as being closely apposed to the brain and spinal cord. the pia is separated from the actual brain tissue, however, by a thin
membrane composed of neuroglial processes that adhere to the thin reticular and elastic fibers of the pia and form a physical barrier at the periphery of the cns. A sheath of pial cells covers the rich vascular supply of the pia, which is replaced by neuroglial cells as these vessels penetrate the nervous tissue.
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127
cLINIcAL coNSIDERATIoNS
Tumors of the meninges, known as meningiomas, are most often slow-growing and benign. They produce possibly serious clinical manifestations, however, such as brain compression or increasing intracranial pressure.
Meningitis, an inflammation of the meninges, may be caused by bacteria or by viruses that have gained access to the CSF. Viral meningitis is not very dangerous; however, bacterial meningitis is not only a very hazardous condition, but it is also highly contagious. The pathogen may gain initial entry through the nose, ear, or throat, and can be spread by the exchange of respiratory secretions via coughing and kissing. The onset of meningitis is characterized by fever, stiff neck, nausea, and vomiting. Meningitis is diagnosed by the examination of the CSF obtained by lumbar puncture, and an antibiotic regimen is used to treat the disease. Vaccines are now available for protecting against some of the common bacteria that cause meningitis.
The blood-brain barrier (BBB) is exceedingly discriminating in permitting passage of substances from the bloodstream into the CNS. It prevents
most therapeutic drugs, many antibiotics, toxins, and certain neurotransmitters including dopamine from entering the neural tissue. Perfusion of a hypertonic solution of mannitol may alter the tight junctions of the BBB sufficiently for a short time permitting the passage of therapeutic drugs.
Another method of bypassing the BBB is the binding of the therapeutic drug to antibodies against transferrin receptors located in the endothelial cells of the capillaries, facilitating their transport into the CNS.
Certain diseases or conditions that affect the CNS, such as stroke, tumors, and infections, alter the BBB by reducing its functionality and
permitting the entry of toxic substances and unwanted metabolites into the neural tissue.
The subarachnoid space is a real space filled with CSF, but the subdural space, located between the dura and the sheetlike layer of the arachnoid that contacts the dura, is only a potential space. It may become a real space after injury, however, when bleeding forces the two layers apart; this condition is called a subdural hemorrhage.
Figure 9.14 the skull and the layers of the meninges covering the brain. (From Gartner LP, Hiatt JL: Color Textbook of Histology, 3rd ed. Philadelphia, Saunders, 2007, p 212.)
Scalp Skull Dura mater Subdural space Arachnoid membrane
Subarachnoid space Vein Artery
Pia mater Brain
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128 bLooD-bRAIN bARRIER
endothelial cells of the continuous capillaries located in neural tissues form tight junctions with each other, establishing the blood-brain barrier (BBB), which limits the ability of blood-borne mate- rial to enter the confines of the cns.
• certain molecules, such as o2, co2, water, and small lipids, can easily pass through the BBB.
• Most other substances, such as glucose, nucleosides, and amino acids, have to be transported by carrier proteins and ion channels that are specific for them.
• still other materials pass through this barrier by the use of receptor-mediated transport.
the BBB is reinforced by astrocytes whose pro- cesses form end-feet that completely surround the basal lamina of the capillaries located in the cns.
the cylindrical sheath fashioned by these end-feet form the perivascular glia limitans. Astrocytes also function in transporting metabolites from the capil- laries to the neurons and in scavenging K+ ions and neurotransmitters from the extracellular spaces sur- rounding the neurons and their processes.
cHoRoID PLExuS
the choroid plexus, composed of tufts of highly vascularized pia mater surrounded by cuboidal epen- dymal cells, project into the ventricles of the brain and produce approximately 50% of the csF. it is unknown where in the brain the remaining half of the csF is produced. csF fills the ventricles of the brain, the central canal of the spinal cord, and the subarachnoid spaces.
cerebrospinal fluid
the CSF is a clear, protein-poor but electrolyte-rich fluid that has a scant amount of lymphocytes and other cells (table 9.4). Because csF is formed on a continuous basis of 0.2 to 0.6 ml/min and is trans- ferred into the dural venous sinuses by the arachnoid villi at the same rate, its formation and resorption acts as a pump that facilitates its circulation through the ventricles of the brain, central canal of the spinal cord, and subarachnoid spaces. this fluid functions in supporting the metabolic activities of the cns, and by acting as a shock absorber diminishes sudden forces that may act on the brain and spinal cord.
cEREbRAL coRTEx
the cerebrum consists of two hemispheres whose periphery is composed of gray matter, the cerebral cortex, which overlies the thick layer of white matter located deeper within the cerebrum. the cerebral cortex is folded into elevated areas called gyri that are separated from each other by depressions called sulci.
• the cerebrum has a plethora of functions, including memory, learning, integration of sensory input, analysis of information, initiation of motor response, and thought processing.
• the cerebral cortex is composed of six
horizontally arranged layers; the neurons in each layer possess distinct morphologic characteristics specific to that layer (table 9.5).
• the outermost layer lies just deep to the overlying pia mater, and the sixth layer contacts the white matter of the cerebral cortex.
• All of the layers contain specific neurons and neuroglia.
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Table 9.4 COMPARISON OF SERUM AND 129 CEREBROSPINAL FLUID (CSF)
Constituent Serum CSF
White blood cells (cells/ml) 0 0–5
Protein (g/l) 60–80 negligible
glucose (mMol/l) 4–5.5 2.1–4
na+ (mMol/l) 135–150 135–150
K+ (mMol/l) 4–5.1 2.8–3.2
cl− (mMol/l) 100–105 115–130
ca++ (mMol/l) 2.1–2.5 1–1.4
Mg++ (mMol/l) 0.7–1 0.8–1.3
ph 7.4 7.3
From gartner lP, hiatt Jl: color textbook of histology, 3rd ed. Philadelphia, saunders, 2007, p 215.
Table 9.5 LAYERS OF THE CEREBRAL CORTEX
Layer Layer Name Neuron Cell Types*
1 Molecular horizontal cells
2 external granular tightly packed granule cells
3 external
pyramidal large pyramidal cells 4 internal granular Pyramidal cells, small
granule cells; thin layer, high cell density 5 internal pyramidal large pyramidal cells; low
cell density 6 Multiform Martinotti cells
*All layers house neuroglia.
cLINIcAL coNSIDERATIoNS
Because CSF is produced in a continuous fashion, blockage of the ventricles or less than optimal functioning of the arachnoid villi results in enlargement of the ventricles, a condition known as hydrocephalus. This disorder has severe consequences because the excess CSF in the enlarged ventricles exerts pressure on the brain.
Because the fontanelles and the bony sutures in the skull are not yet fused in fetuses and
neonates, this condition results in enlargement of the head, mental impairment, malfunctioning muscles, and eventual death without treatment.
alzheimer’s disease, the most common neurodegenerative disease, affecting about 5 million individuals in the United States, results in dementia that is progressive and terminal. It is usually diagnosed in individuals older than 65
years, although the onset may have occurred years earlier. The most common early symptom is memory loss followed by confusion, irritability, aggression, and mood swings. Later symptoms include breakdown of language, long-term memory loss, decline of senses, general withdrawal, loss of bodily functions, and finally death. Although the cause is not clearly understood, it is characterized by the loss of neurons and synapses mainly within the cerebral cortex followed by gross atrophy of the individual cerebral lobes. Autopsies have shown that patients with Alzheimer’s disease develop amyloid plaques and neurofibrillary tangles within the brain that, as they continue to expand, involve a greater number of neurons, rendering them nonfunctional.
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130 cEREbELLAR coRTEx
the cerebellum comprises two lateral hemispheres and a central, connecting portion, known as the ver- mis. the peripheral layer of the cerebellum, the cer- ebellar cortex, is composed of gray matter that over lies the deeper white matter. the cerebellar cortex is responsible for maintaining balance during all phases of posture and coordinates voluntary muscle activ ity and muscle tone. the cerebellar cortex has three separate layers:
• Molecular layer—composed mainly of dendrites of Purkinje cells and unmyelinated axons from the granular layer, and some stellate cells and basket cells
• Purkinje cell layer—composed of large Purkinje cells (unique to the cerebellum) whose arborized dendrites are observed in the molecular layer, whereas their myelinated axons project into the white matter
• Granular layer—composed of crowded nuclei of small granule cells and glomeruli (cerebellar islands) representing synapses between axons entering the cerebellum and the resident granule cells.
Purkinje cells have only an inhibitory output, and they process and integrate simultaneous infor- mation from hundreds of thousands of excitatory and inhibitory synapses before forming a response.
Purkinje cells release only gABA as their neurotrans- mitter substance, and they are the only cells of the cerebellum whose processes and responses extend outside the cerebellum.