Cellular Pathology of

the Central Nervous System

Dr. Salmeen Abdulla Saleh

 Central Nervous System
The principal functional unit of the central nervous system (CNS) is
the neuron. Of all the cells in the body, neurons have a unique ability
to receive, store, and transmit information. Neurons of different
types and in different locations have distinct properties, including
functional roles, distribution of their connections, neurotransmitters
used, metabolic requirements, and levels of electrical activity at a
given moment. A set of neurons, not necessarily clustered together in
a region of the brain, may thus show selective vulnerability to various
insults because it shares one or more of these properties. Since most
mature neurons are incapable of cell division, destruction of even a
small number of neurons essential for a specific function may leave
the individual with a neurologic deficit. Stem cell populations in the
brain may represent a potential mechanism for repair after injury.[1]
The CNS is affected by a number of unique neurological disorders,
and also responds to common insults (e.g., ischemia, infection) in a
manner that is distinct from other tissues
 Reactions of Neurons to Injury.
The principal patterns of neuronal injury are the
following:
1.Acute neuronal injury (“red neurons”) refers to a
spectrum of changes that accompany acute CNS
hypoxia/ischemia or other acute insults and reflect cell
death, either necrosis or apoptosis . “Red neurons” are
evident with hematoxylin and eosin (H&E) preparations at
about 12 to 24 hours after an irreversible hypoxic/ischemic
insult. The morphologic features consist of shrinkage of
the cell body, pyknosis of the nucleus, disappearance of the
nucleolus, and loss of Nissl substance, with intense
eosinophilia of the cytoplasm.
Acute ischemic injury causes
diffuse eosinophilia of
neurons, which are beginning
to shrink.
2, Subacute and chronic neuronal injury
(“degeneration”) refers to neuronal death occurring as
a result of a progressive disease process of some
duration, as is seen in certain slowly evolving neurologic
diseases . The characteristic histologic feature is cell
loss, often selectively involving functionally related
groups of neurons, and reactive gliosis. When the
process is at an early stage, the cell loss is difficult to
detect; the associated reactive glial changes are often the
best indicator of the pathologic process. For many of
these diseases, there is evidence that cell loss is because
of apoptosis.
3.Axonal reaction refers to the reaction
within the cell body that attends regeneration
of the axon; it is best seen in anterior horn
cells of the spinal cord when motor axons are
cut or seriously damaged. There is increased
protein synthesis associated with axonal
sprouting. This is reflected in enlargement
and rounding up of the cell body, peripheral
displacement of the nucleus, enlargement of
the nucleolus, and dispersion of Nissl
substance from the center to the periphery of
the cell (central chromatolysis).
4.Neuronal damage may be associated with a wide range
of subcellular alterations in the neuronal organelles and
cytoskeleton. Neuronal inclusions may occur as a
manifestation of aging, when there are intracytoplasmic
accumulations of complex lipids (lipofuscin), proteins, or
carbohydrates. Abnormal cytoplasmic deposition of
complex lipids and other substances also occurs in
genetically determined disorders of metabolism in which
substrates or intermediates accumulate. Viral infection
can lead to abnormal intranuclear inclusions, as seen in
herpetic infection (Cowdry body), cytoplasmic
inclusions, as seen in rabies (Negri body), or both
nucleus and cytoplasm as in cytomegalovirus (CMV)
infection.
5.Some degenerative diseases of the CNS are
associated with neuronal intracytoplasmic
inclusions, such as neurofibrillary tangles of
Alzheimer disease and Lewy bodies of
Parkinson disease; others cause abnormal
vacuolization of the perikaryon and neuronal
cell processes in the neuropil (Creutzfeldt-
Jakob disease). These aggregates are highly
resistant to degradation, contain proteins with
altered conformation,
Reactions of Astrocytes to Injury.
The astrocyte derives its name from its star-shaped appearance.
These cells have multipolar, branching cytoplasmic processes that
emanate from the cell body and contain the glial fibrillary acidic
protein (GFAP), a cell type–specific intermediate filament .
Astrocytes act as metabolic buffers and detoxifiers within the
brain. Additionally, through the foot processes, which surround
capillaries or extend to the subpial and subependymal zones, they
contribute to barrier functions controlling the flow of
macromolecules between the blood, the cerebrospinal fluid (CSF),
and the brain. Gliosis (or astrogliosis) is the most important
histopathologic indicator of CNS injury, regardless of etiology,
and is characterized by both hypertrophy and hyperplasia.
Astrocytes and their processes. Immunohistochemical
staining for GFAP reveals astrocytic perinuclear
cytoplasm and well-developed processes (brown).
Reactions of Other Glial Cells to Injury.
In contrast to astrocytes, oligodendrocytes and
ependyma do not participate in the active response to
CNS injury and show a more limited repertoire of
reactions.
Microglia are respond to injury by (1) proliferating;
(2) developing elongated nuclei (rod cells), as in
neurosyphilis; (3) forming aggregates about small foci
of tissue necrosis (microglial nodules); or (4)
congregating around cell bodies of dying neurons
(neuronophagia). In addition to resident microglia,
blood-derived macrophages are the principal
phagocytic cells present in inflammatory foci.
Cerebral Edema, Hydrocephalus, and
Raised Intracranial Pressure and
Herniation
Hydrocephalus refers to the accumulation of excessive
CSF within the ventricular system . Most cases occur as a
consequence of impaired flow and resorption of CSF; only
rarely is overproduction the cause of hydrocephalus (e.g.,
with tumors of the choroid plexus). An increased volume
of CSF within the ventricles expands them and can elevate
the intracranial pressure.
When hydrocephalus develops in infancy before closure of
the cranial sutures, there is enlargement of the head,
manifested by an increase in head circumference.
Hydrocephalus developing after this period, in contrast, is
associated with expansion of the ventricles and increased
intracranial pressure, without a change in head
circumference.
Hydrocephalus. Dilated lateral ventricles seen in a coronal
section through the midthalamus.
 RAISED INTRACRANIAL
PRESSURE
When the volume of the brain increases beyond
the limit permitted by compression of veins and
displacement of CSF, the pressure within the
skull will increase. Most cases are associated
with a mass effect, either diffuse, as in
generalized brain edema, or focal, as with
tumors, abscesses, or hemorrhages. Elevated
intracranial pressure may also reduce perfusion
of the brain, further exacerbating cerebral
edema.