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Neuropathology
Roberta
J. Seidman, M.D., Associate Professor.
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Normal
brain
| A general
appreciation of normal brain gross and microscopic features
is a prerequisite for learning about pathology of the central
nervous system. When you are looking at pathological specimens
in the later chapters, these images can provide a reference
for comparison. |
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THE
MENINGES
The meninges consist of three layers. The outermost is called
the dura mater, also known as the pachymeninx (pachy
= thick). It consists of two fused layers of dense fibrous connective
tissue. The external layer is adherent to the skull and actually
forms the periosteum. In older individuals, the dura can fuse
with the skull.
In several locations, the two layers separate and form the dural
sinuses, the major venous channels of the brain. The dura is
folded in the midline to form the falx cerebri, which
incompletely separates the two cerebral hemispheres. The other
major fold is the tentorium cerebelli, which separates
the cerebellum from the cerebral hemispheres. The tentorium
stretches over the top of the posterior cranial fossa. When
considering the location of pathological processes, it is common
practice to separate them into supratentorial and infratentorial
processes.
The potential space located between the dura and the bones of
the cranium is known as the epidural space. The potential space
between the dura and the underlying meninges and brain is called
the subdural space. In life, there are no actual spaces, but
these are tissue planes that may be separated.
The arachnoid and the pia mater together form the leptomeninges
(lepto = slender). The arachnoid, a thin membrane, is connected
to the underlying pia via wispy connective tissue fibers that
resemble spider webs; these give the arachnoid ("spider-like")
its name. The arachnoid is loosely applied to the brain and
is normally almost transparent.
The pia is a delicate membrane that closely covers the brain
surface, following all of its convolutions and coating the penetrating
arterioles and venules to the point where they become capillaries.
In the spinal canal, the pia forms the denticulate ligaments
and the filum terminale. The pia is closely related to the peripheral
layer of astrocytic end feet. Together, they form the pia-glial
limiting membrane of the central nervous system. The pia is
intimately connected to the surface of the brain and spinal
cord, but some pathological processes, for example, certain
brain tumors, can spread within and along the subpial space.
The space between the pia and arachnoid is the subarachnoid
space, which is filled with cerebrospinal fluid (CSF). The brain
and spinal cord are thus suspended from the dura-arachnoid by
the arachnoid trabeculae and are floating in a bath of CSF.
The subarachnoid space also contains the superficial cerebral
arteries and veins. In areas where the brain and spinal cord
surface is relatively far from the dura-arachnoid, the subarachnoid
space is enlarged to form cisterns. The largest subarachnoid
cistern surrounds the medulla and the base of the cerebellum.
This is the cerebello-medullary cistern, or the cisterna
magna. |
THE
BRAIN
The brain has five major anatomic divisions that are based upon
the structure of the developing brain. These are:
1.
the telencephalon, which includes the cerebral hemispheres
and the deep structures known collectively as the basal
ganglia
2. the diencephalon, which is composed predominantly
of the thalamus, epithalamus and hypothalamus
3. the mesencephalon, or midbrain
4. the metencephalon, consisting of pons and cerebellum
5. the myelencephalon, which is the medulla |
EXTERNAL FEATURES
OF THE BRAIN
When looking at the brain, the cerebral hemispheres are the
most prominent structures of the brain. The cerebral cortex,
which is located on the surface is highly convoluted. This allows
for the packing of a great surface area in a small space (the
cranial cavity). In other animals, such as rats, rabbits and
frogs, there has not been such a great expansion of the cortex
and these brains are smooth (lissencephalic). The elevated folds
are called gyri, while the furrows between them are called sulci.
Very deep sulci are also referred to as fissures. While there
is some inter individual variability in the patterns of gyration
and sulcation, there is actually a striking consistency in the
pattern.
| Using
the images of the lateral
and superior
views of the cerebral hemispheres, you should review the
locations of the Sylvian (lateral) fissure and the central
sulcus . The precentral gyrus (with primary motor
cortex) and the postcentral gyrus (with primary
somatosensory cortex) are anterior and posterior to the
central sulcus, repectively. The important language areas,
Broca’s and Wernicke’s areas in the dominant hemisphere.
Appreciate the normal appearance of gyri and sulci. |
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| On
the inferior
view of the brain, identify the optic chiasm and
mammillary bodies. Other than their distal stumps,
the optic nerves are not present in the specimen. Identify
the pons, medulla and cerebellum. |
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Internal
neuroanatomical landmarks and highlights of normal histology
of brain
| In
the coronal sections 1,
2,
& 3
review the locations of the basal ganglia, which include
the caudate nucleus, the putamen and the globus pallidus.
Identify the thalamus, amygdala and hippocampus. Examine
the appearance of the subcortical white matter, corpus
callosum and internal capsule. Note the locations, size
and shape of the lateral and third ventricles. The lateral
ventricles in this brain are mildly dilated. |
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The parenchymal cells of the central nervous system are neurons
and glia. The important cell types to examine are neurons, particularly
cerebral cortical pyramidal neurons, oligodendroglia, astrocytes,
ependymal cells and choroid plexus epithelium. The latter four
cell types are glia or derived from glia. One should also examine
leptomeninges and blood vessels.
| View
a histological section of Cerebral
cortex with subcortical white matter. This is stained
with Hematoxylin and Eosin (H&E), a routine, general
purpose histological stain used for basic examination
of tissue. Note that the cortex is a slightly paler pink
than the more deeply staining subcortical white matter.
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| First
view the normal arachnoid
and the subarachnoid
space that contains normal superficial
blood vessels that supply the brain. Identify the
cerebral
cortex that contains six layers of neurons. Layer
1 is the most superficial and layer 6 is deepest. Layers
III and V are richest in pyramidal neurons. Note the normal
texture of the neuropil between the neurons. Examine the
cerebral
cortex at higher power and identify pyramidal
neurons with their large nuclei and prominent nucleoli.
Notice the basophilic (blue) character of the cytoplasm
of these cells, which is a characteristic feature of neurons.
Many of the pyramidal neurons have small round nuclei
associated with them. These round nuclei are known as
satellite
cells, which are oligodendroglial cells in gray matter.
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| The
subcortical
white matter is largely composed of axons and oligodendroglia.
In the white matter, the oligodendroglia are the myelin-forming
cells of the central nervous system. Note their characteristic
round nuclei, surrounded in many cells by a clear rim.
This characteristic “fried-egg” appearance of
oligodendroglial cells is actually an artifact of delayed
fixation. It is an artifact that is very useful for the
identification of these cells. Notice the cellularity
and texture of normal white matter. Look at normal blood
vessels. |
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| Look
at a section of basal
ganglia at low and higher magnifications. The caudate
and putamen are histologically identical because of their
common developmental origin. The caudate is easy to identify
because it is located in the lateral wall of the lateral
ventricle, so it will always have an ependymal lining.
Examine the ependyma,
which consists of a single layer of ciliated cuboidal
epithelium at the ventricular surface of the brain. It
also lines the central canal of the spinal cord. The central
canal is normally not an open structure in adults as it
is in the developing central nervous system. Examine the
caudate
and putamen
. The globus
pallidus has a different texture and different cellular
composition than the caudate and putamen, which goes along
with its differing neurophysiological function. |
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| The
hippocampal
formation has three components: the dentate gyrus,
the hippocampus proper (also called Ammon’s horn)
and the subicular complex. The dentate
gyrus contains a layer of small neurons. Ammon’s
horn has four sections, CA1-4. The CA1
region is important to recognize because of the particular
vulnerability of the neurons in the pyramidal layer to
global hypoxic-ischemic events. |
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| The
midbrain,
or mesencephalon, is the location of the cerebral
aqueduct (of Sylvius), the corpora quadrigemina (superior
and inferior colliculi), the substantia
nigra and the cerebral
peduncles. Note the normal appearance of the pigmented
neurons of the substantia nigra. The oculomotor nuclei
are located here and the oculomotor nerves course ventrally
to exit at the interpeduncular fossa. The trochlear nuclei
and nerves are located in caudal midbrain. |
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| The
pons
has a tegmentum
and base.
The locus ceruleus is an important pigmented noradrenergic
nucleus located lateral to the fourth
ventricle in the tegmentum. The base contains the
crossing
pontocerebellar fibers that form the middle cerebellar
peduncle and the corticospinal tracts run through the
base of the pons on their way to the spinal cord. The
cranial nerves and nuclei of the pons are V- VIII. |
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| A
section of spinal
cord reveals the dorsal and ventral roots, the dorsal
horn, the ventral
horn which contains the spinal motor neurons and the
white matter tracts located at the periphery of the cord.
Note the typical appearance of a motor
neuron, with its prominent nucleolus in the nucleus
and the basophilic (blue in H&E stain) tigroid appearance
of its cytoplasm, which is due to the presence of abundant
ribosomes needed in the manufacture of proteins |
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