NERVOUS TISSUE

Winston S. Abena, MD., FPASMAP, COSH

Saint Paul University Philippines
School of Medicine
 the nervous system is widely distributed in the body
comprising the entire mass of nervous tissue
 basically, the NS consists of tissue which receive stimuli
from both the internal & external environments; upon
receiving the stimulus, various forms of energy are
transduced to electrical energy by specialized structures
called the receptors  nervous centers  produces
appropriate responses in effector organs
 it also include structural areas for all conscious experience;
all functions are performed by an intercommunicating
network of specialized cells called neurons which
constitute most sensory receptors, the conducting
pathways & the sites of integration & analysis; together
with their supporting or neuroglial cells & associated
extracellular material, they form the nervous system
Functions:
1. Its essential function is communication, based upon 2
fundamental attributes of protoplasm: irritability or
the capacity to react to various physical & chemical
agents, and conductivity or the ability to transmit the
resulting excitation from one locality to another.
2. It provides the structural & chemical basis of
conscious experience; it furnishes the mechanism &
regulation of behavior & the maintenance of
personality.
3. Some nerve cells, like the hypothalamic nuclei of the diencephalon,
possess secretory capabilities with an endocrine nature, which carries
out its integrative function by means of hormones; the secretory
products of such neurons are released from axon terminals into a
perivascular space, transported into the lumen of the vessel and carried
by the blood to the particular target organ
Functionally, it is divided into somatic & autonomic parts, with
central & peripheral divisions:
a. somatic portion – concerned with structures derived from the
embryological somites, i.e. muscles, bones, and skin; muscles derived from
branchial arches are included in this part because histologically, the
muscles of the 2 groups are identical
- is involved in voluntary functions
b. autonomic portion – concerned with the innervation of the smooth
muscle, cardiac muscle, & the glands of the body; their functions are
independent of the rest of the NS to a great extent
- is involved in many involuntary functions
Anatomically, it is divided into 2 parts: the central
nervous system (CNS or neuraxis), consisting of
the brain & spinal cord located in the cranium &
vertebral canal; the peripheral nervous system
(PNS), which comprises all nervous tissue outside
the brain & spinal cord functions to keep the other
tissues of the body in communication with the NS
– it is made up of nerves emerging from the CNS &
small encapsulated aggregations of nerve cell
bodies called ganglia.
Histologically, the entire NS merely consists of
variations in the arrangement of neurons & their
supporting tissues.
 Neuron
 cells primarily involved in its special function
 structural unit of the NS
 neurons/neurocytes/nerve cells
 it consists of a cell body together with all of its processes up to
their peripheral terminations; these cells are related with other
nerve cells by their processes; their point of contact are termed
synapses
The Neuron
 the nervous tissue also exhibits characteristic appositional or
junctional complexes consisting of local specializations of the
surfaces of adjacent cells; its function is to maintain the position of
the neurons & to stabilize those relations of their processes
necessary to their signaling function
 it can occur inside or outside in the PNS where they are termed
ganglion cells
 the study of the neuron can histologically be divided into the nerve
cell & the nerve fiber; the nerve cell includes the cell body or cyton
(perikaryon) with the proximal parts of its processes (dendrons &
axons) that are located close to the vicinity of the cell body; the
nerve fiber comprises the continuation of these cell processes
extending beyond the vicinity of their cell bodies to go out of the
gray mater to constitute part of the white mater & PNS
the processes extending from the perikaryon are
specialized for 3 primary functions:
1. Reception of various stimuli – generally, the function of
the dendritic zone (receptor portion) of the neuron
including those areas of the cell body or the axon that
receives signals from other cells
2. Conduction – of the nerve impulse (action potentials)
to regions distant from the receptive area; this is
generally the function of the axon, but dendrite regions
& cell bodies may also propagate impulses
3. Synaptic transmission – of the signal to subsequent
neurons in the neural pathways or to muscle or gland;
this effector function generally occur in the nerve
terminals, where neuro-transmitters are released
it can also be coupled by gap (communicating)
junctions sometimes called electrotonic synapses
Distribution:
 are found in the gray mater of the CNS, including the different small
areas of gray mater embedded in the white mater of the brain like
the basal ganglia & in the different ganglia (cerebrospinal &
sympathetic) of the peripheral nerves; clusters of nerve cell bodies
in the gray mater are called Nuclei, which are not to be confused
with cellular nuclei as they represent functional aggregates of
neurons
Description:
 it is usually large & complex in shape
 it consists of a cell body (perikaryon/soma) with an axon & usually
several dendrites
 its size varies from 4 – 100 micra in dia. such as the multipolar
neurons in the central gray horn of the spinal cord; the total
number of nerve cells in the body has never been accurately
estimated, but there are probably 14 billion in the cerebral cortex
alone
Varieties & Distribution of Neurons:
distinguished based on the number, length,
thickness, & mode of branching of the processes,
and on the basis of the shape, size, & position of
the cell body as well as of the synaptic
relationships
a. Golgi type I neurons – have long axons that leave
the gray mater traverse the white mater
terminating at some distance in another part of
the gray mater
- this includes the neurons that contribute to the
formation of the peripheral nerves & those whose
axons form long fiber tracts of the brain & spinal
cord.
b. Golgi type II neurons/association neurons – have
relatively short axons & does not have the region of the
gray mater where its cell body lies
- they are especially numerous in the cerebral & cerebellar
cortices & in the retina.
c. Purkinje cells – these are big pyriform cells found in the
middle layer of the cerebellar cortex.
d. Unipolar neurons – are nerve cells with only one process
- true unipolar neurons are rare (except in early embryonic
stages)
*all neurons of the craniospinal ganglia are first bipolar
but during development, the opposing processes combine
into a single process & are thus termed pseudo-unipolar
- the adult cell body is globular or pear-shaped
- a single process arises & divides like the letter T; one
branch is directed to the periphery & the other courses in a
posterior nerve root to the CNS.
e. Bipolar neurons – characterized by a process projecting from each
end of the fusiform cell body
- are typically found in the retina, vestibular & cochlear ganglia, and
in the olfactory nasal epithelium.
f. Multipolar neurons – have more than 2 processes but only one
axon
Stellate/star-shaped nerve cells – includes the motor nerve cells of
the ventral gray mater of the spinal cord & of the motor nuclei of
the brain stem
g. Pyramidal neurons – are characteristic cells present in the cerebral
cortex; an exceptionally large neuron is called the pyramidal cell of
Betz.
h. Anaxonic neurons – are cells that do not possess axons; they have
both receptor & effector regions on their dendrites; they do require
no conductile portion to convey receptor influence to distant
regions
e.g. amacrine cells of the retina
Functionally, they can also be classified as:
a. Motor neuron – controls the effector organs such as
muscle & glands
b. Sensory neuron – receives sensory stimuli (both
exteroceptive & interoceptive)
c. Internuncial neurons/interneurons – it connects other
neurons to establish complex functional circuits or
chains of neurons
Each ganglion, nucleus or cortical area, is
therefore, composed of a:
1. characteristic variety of neurons in different
proportions, each cell type designated to meet its
special functional requirements
2. “Neuropil” which is a complex feltwork of dendritic,
axonal & glial processes
it has a number of distinctive cytological
characteristics:
1. Perikaryon (Soma)
portion of the nerve cell surrounding the nucleus
& is vital for the survival of the entire cell
has a receptive function receiving stimuli
generated in other nerve cells
main role: the trophic or nourishing center of the
cell, supplying organelles & macro-molecules to its
processes
it is usually large up to 135 microns or micrometer
in dia. although some are only 4 μm
a thin plasma membrane surrounds the nerve cell
body/cyton; its neuroplasm is filled with organelles
that includes neurofibrils, chromophilic substance
or Nissl bodies, mitochondria, centrosome, &
various inclusions (fat, glycogen, lipofuscin &
melanin pigment)
Cytoplasmic organelles:
a. Neurofibrils & Microfibrils
Neurofibrils – are well developed in large neurons
appearing as slender, interlacing threads when
impregnated with silver
EM: they are formed by neurofilaments which
lie parallel to the long axis of the process; each
filament is actually a tubule with a dense wall &
clear center
 Microtubules (Neurotubules) – are often
abundant, disposed in areas around the
nucleus & continuing into the processes
- they are 25 nm in diameter, while the
neurofilaments are 10 nm in diameter,
appearing similar to intermediate filaments
found elsewhere
b. Nissl substance – they are prominent in the
cytoplasm when stained with basic aniline dyes
(toluidine blue, thionin, or cresyl violet)
- they appear as deeply basophilic masses or
blocks in the cell body
Nerve Cell Body with dark staining Nissl
- one of its principal constituents is
ribonucleoprotein, it is found in the perikaryon &
in the proximal parts of the dendrites of all large &
small neurons (but not in the axon & axon hillock)
- they are coarser & more abundant in large motor
nerve cells of the CNS; smallest in the sensory
nerve cells of the root ganglia; & intermediate in
size in the sympathetic ganglion cells
- EM: it is composed of clusters of ER with
ribosomes bound to the outer surface of
cisternae, or as free ribosomes; basophilia
depends on the presence of RNA in the
ribosomes; have the presence of sub-surface
cisternae which are distinctive characteristic of
neurons visible only in EM
 - they seem to have nutritive function to the cell & its
processes
- they change their appearance under different
physiological conditions (rest or fatigue); its amount is
diminished by fatigue & nerve injury, recovered after a
period of rest
- dissolution of Nissl bodies, Chromatolysis
c. Golgi Apparatus – present in all nerve cells
- appears as a network of irregular, wavy strands that are
coarser than the network of neurofibrils
- EM: appears as multiple clusters of closely apposed,
flattened cisternae arranged in stacks & surrounded by
small vesicles; it is limited to the perikaryon; its
prominence in neurons probably relates to the fact that
much of the protein manufactured by the neuron like
secretory cells, is channeled through the Golgi region
d. Mitochondria – numerous & elongated, they are
generally smaller than those of non-nervous
tissues
- its number varies from cell to cell & in different
parts of the cells; they are especially numerous in
axon endings or terminal boutons & in the region
of the nodes of Ranvier
- their fine structure reveals 2 peculiarities of
unknown significance; the cristae run of both
tubular & lamellar types parallel to the long axis of
the mitochondria & they do not show
mitochondrial granules
e. Centrosome – with its pair of centrioles is
present only in young neurons; it is seldom
observed in adult neurons (although in EM may
reveal occasional presence)
f. Lysosomes – primary lysosomes are common, usually located near
the Golgi apparatus
- they are associated with hydrolysis of end products of cellular
metabolism & with degradation of lipids
g. Cytoplasmic Inclusions
1. Pigment granules (melanin) – they are encountered in the neurons of the
substantia nigra of the midbrain, the locus ceruleus near the IV ventricle,
the dorsal motor nucleus of the X nerve, & the spinal sympathetic ganglia
& cells of the reticular formation
- its significance is unknown
2. Lipofuscin – golden brown pigment granules that increases with advancing
age, displacing the nucleus & organelles to one side of the nerve cell
- they are harmless metabolic byproducts
- they are apparently secondary lysosomes representing the end product of
lysosomal activity during the long life of the nerve cell
3. Lipid droplets & Iron-containing granules – are found in neurons of
substantia nigra & the globus pallidus of the nucleus lentiformis
- its number increases as the individual grows older
Sympathetic ganglion w/ lipofuscin pigment
4. Glycogen granules – seen only in embryonal neurons & neuroglia
5. Granules of neurosecretory neurons (hypothalamus) – are about 10 – 30
nm in dia. containing the hormones vasopressin & oxytocin, and their
carrier peptide neurophysiors
- they are transported via the axon to the neurohypophysis where their
hormonal contents are discharged & diffuse into the blood stream
2. Nucleus
 it is large (up to 20 μm in dia.), rounded & centrally
situated in the soma
 there is a single prominent nucleolus with very fine
chromatin particles; the large size of the nucleolus
probably is caused by the high rate of protein synthesis
which is necessary to maintain the protein level in the large
cytoplasmic volume in the cell body
 nuclei of nerve cells appear empty & pale or “vesicular”
when stained with basic dyes; this large, pale vesicular
nucleus with a prominent dark, staining nucleolus is often
referred to as having the “owl’s eye” or “fish eye”
appearance
 sex chromatin (Barr body) may be present as a nucleolar
satellite in the female, representing the condensed
chromosome & situated at the inner surface of the nuclear
membrane
3. Nerve Cell Processes
these are cytoplasmic extensions of the nerve cell
body, developed to provide conduction pathways
& to provide greater surface areas for contact
there are 2 kinds of cytoplasmic processes:
a. dendrites (dendrons)
b. axons
A. Dendrite
- is a process with a broad base, tapering gradually
along its length towards the ends
- its cytoplasmic content is similar to that of the cell
proper, being a direct extension of the perikaryon
- they are relatively short & are confined to the
immediate vicinity of the body
- each may divide into primary, secondary, tertiary & higher orders of
branched of different shapes & sizes
- its surface is covered with numerous minute, thorny spines or
“gemmules” (dendritic spines) often serving as sites of synaptic
content
- they carry impulses toward the cell body & are therefore,
cellulipetal or afferent processes
- there may be several dendrites to a nerve cell, rarely, there is only
one
- they constitute the felt-like “neuropil” of the CNS
- EM: presence of mitochondria, Nissl bodies, long
parallel tubules (neurotubules or microtubules) &
neurofilaments; the ER, Golgi complex, tubules &
filaments become scanty & towards the
termination may disappear
- functionally, its microtubules are involved with the
transport of organelles (mitochondria) & proteins
from the perikaryon to the terminations of the
dendrites; this transport can be inhibited by drugs
such as colchicine & vinblastine, that causes
microtubule breakdown
- they display local changes in membrane potential
in response to impulses received
B. Axon (axis cylinder)
- there is only one axon to each neuron
(occasionally no axon at all, i.e. amacrine cells of
retina)
- it is continued as the axis cylinder of a nerve fiber
- its plasma membrane is called axolemma
- it arises from a conical elevation on the perikaryon
devoid of Nissl bodies, called the axon hillock or
implantation cone
- the portion of the axon between the cell body &
the point at which there is some form of axonal
attachment (such as myelin) is termed as the
initial segment
- it may arise from the stem of a principal dendrite
- it does not contain Nissl bodies, and usually is
thinner & much longer than the dendrites of the
same neuron
- it contains more neurofibrils, so that it appears
more fibrillar than the dendron – they are
embedded in a small amount of neuroplasm called
axoplasm
- EM: presence of hollow neurofilaments,
mitochondria, agranular ER & microtubules
- the branches of the axon are given off from the
cell body; they arise at right angles from the nodes
of Ranvier; these branches are termed the axon
collaterals
- gemmules are not very characteristic
 TEM of Nerve Cell Body and Axon

Nu =
nucleus

Ax =
Axon

Fi = neurofilaments; Re = RER; Go = golgi; Mi = Mitochondria

- the axon & its branches end in a terminal
arborization of the remaining constituent
neurofibrils or terminally, it ends in twig-like
branching called the telodendria (touches the cell
body, dendrites or axons of 1 or more neurons at
synapses) – when they are numerous & surrounds
the neuron on which they terminate in a basket-
like arrangement
- the plasmalemma or axolemma covering an axon
is continuous with that of the nerve cell body
- through its ending, transmits nerve impulses to
other neurons or to muscle fibers & gland cells
- it has a prominent sheath called “myelin”, this
appears black in tissue fixed in osmium tetroxide –
it is a part of an ensheathing cell (cell of Schwann)
- new protoplasm are continuously synthesized by
the nerve cell body which flows down the nerve
cell processes at a rate of 1 mm/day to replace
protoplasm used in metabolism (axoplasmic
transport); the protoplasm transported is utilized
for: membrane renewal, neurotransmitter
synthesis & recycling, & exerts trophic effects on
innervated tissue; the material can also be
transported from nerve terminals back along an
axon to the perikaryon termed retrograde
transport
 TEM of Axons (A)

S = Schwann cell; F = fibroblasts; Note lack of RER in axons

C. Ganglia
- a collection of nerve cells located outside the CNS
- 2 main types:
a. Sensory Ganglia – those of the craniospinal group
b. Visceral motor Ganglia – those of the ANS
- its supporting tissue is areolar CT, while that of the
CNS is Neuroglia
- it is composed of nerve cells, nerve fibers & a
supporting areolar CT
- it is termed a ganglion proper when the nerve
cells predominate over the nerve fibers; it is
termed a plexus when the nerve fibers
predominate over the nerve cells; a ganglion,
therefore, has more nerve cells than fibers
Low magnification of a Ganglion
- vary in size, ranging from very small (with a few nerve cell bodies)
to a very large one (with 50,000 or more cells); it has a CT capsule
which may be quite dense around large ganglia; the capsule is
composed of a single layer of small, flattened cells termed
capsule/satellite cells; there are blood vessels that course in the CT
- 2 classifications:
a. Cerebrospinal (craniosacral ganglia)
b. Sympathetic ganglia
Cerebrospinal/Craniospinal Ganglia
• Spinal ganglia are fusiform (spindle-shaped) or
globular swellings situated on the posterior or
dorsal roots of the spinal nerves; Cranial ganglia
have similar swellings found on some of the
cranial nerve
• these are true neurons which are mostly unipolar
in type; its neuroplasm contains small-sized Nissl
bodies that are uniformly distributed; they possess
a single process which divides not far from the cell
body into 2 branches: one proceeding to some
peripheral sense organ & another entering the
brain or development (cells have a typical bipolar
form). In later growth, the processes converge &
fuse forming the T- or Y-shaped
 process termed the dendraxon (characteristic of
adult cell) = these neurons are thus called
“pseudo-unipolar”
• the single process may be relatively short, running
a considerable distance before bifurcating; it may
envelope the cell body of origin in a complex
tangle, resembling a “glomerulus”
• the initial single process & the peripheral and
central branches are myelinated; the perikaryon of
pseudo-unipolar neuron is ensheathed by both
cellular & fibrous CT elements. The inner
investment is made up of:
1. small, flattened epithelium-like “satellite cells”
(capsule cells or amphicytes) similar to neuroglial
cells (oligodendrocytes); they form a mosaic which
completely envelops the neuronal cell body
Cell Body w/ Nissl and surrounding Satellite Cells
TEM of a Cell
Body and
Satellite Cells
(Sat)
2. an outer vascular CT capsule which is continuous
with the endoneurium or sheath of Henle.
• Spinal Ganglion may be classified into:
1. Large clear cells – light staining cells with
vesicular nuclei & fine chromophilic bodies,
usually considered as the typical spinal ganglion
cells; they constitute <30% of the total number
- the Nissl substance is separated into groups by
microtubules & neurofilaments which course
through the cell body & extend into the axonal
process
- majority of the large ganglion cells have axons of
the “intracapsular glomerular” type as the axon is
coiled & looped around the cell body
Spinal Ganglion w/ cell bodies and nerve fibers
2. Small obscure cells – cells that stain more deeply
& diffusely; they comprise about 50 – 75% of the
ganglion cells
- they give rise to unmyelinated fibers, closely
packed Nissl substance; its axons are of the
uncoiled type
- they do not receive synapses as the sensory
ganglion is not an integrative center
Autonomic Ganglia
• these are situated as swellings along the
sympathetic chain & its ramifications, and within
the walls of the organs supplied by the ANS (which
constitutes the intramural ganglia which are small
& devoid of CT capsule)
• their cells are supported by the stroma of the
organ in which they are found; the capsule cells
may be replaced by small spindle-shaped cells
similar in appearance to small fibroblasts
• majority of the nerve cells are multipolar &
stellate in shape
• cells are smaller than those of the craniospinal
ganglia ranging from 15 – 45 μm in dia.
• their dendrites may be coiled to form a glomerulus
situated either within or outside the capsule; in
small ganglia (situated in the walls of the viscera),
a capsule is lacking; capsule cells may be replaced
by small, spindle-shaped cells similar to small
fibroblasts
• their axons are usually unmyelinated & do not show a tendency to
group into distinct fiber bundles; in the adrenal medulla, the
autonomic ganglion cells lack axons & dendrites, they contain
secretory granules of catecholamines
• they contain synapses where the first neurons of the 2 neuron
efferent system form a synapse with the second neuron of the
visceral motor pathway
• has numerous axosomatic & axodendritic synapses; also small,
densely staining interneurons
• cells are mostly motor neurons
a. Sympathetic fibers arise from the cells in the
intermediolateral column of the spinal cord, from T1 – L3
region
b. Parasympathetic fibers arise from III, VII, IX, & X cranial
nerves & from the 2nd, 3rd, & 4th sacral nerves
• many of the larger ganglion cells are adrenergic
EM: they contain small vesicles with a dense core
both in their soma & processes (particularly at the
termination of their axons); they contain the
neurotransmitter noradrenaline/norepinephrine
• few smaller cells contain larger dense-cored
vesicles which probably are dopaminergic; their
contents are released directly into the blood
stream
4. Nerve Fibers
 term applied to long axons but includes all nerve cell processes
 it consists of an axon & sheaths of ectodermal origin
 all nerve fibers (whether in the CNS or PNS), have one or more
sheaths
 the “cellular sheath” in the CNS – is glia with or without myelin
(myelinated or unmyelinated)
 in the PNS – it is neurolemma (sheath of Schwann) with or without
myelin
all peripheral axons are enclosed by a sheath of
Schwann cells that invest the axons almost from
its beginning to its peripheral termination; the
large peripheral axons are also enveloped in a
myelin sheath found within the neurolemma or
nucleated sheath of Schwann; the smallest axons
of peripheral nerves lack a myelin sheath so that
the axons are designated as myelinated or
unmyelinated
it may therefore, acquire both any or more of the
following coverings which have been found to be
closely related under the EM:
a. Myelin sheath
b. Sheath of Schwann (Neurolemma)
Myelin (Medullary Sheath)
• an axon or dendron that arises from the cell body
in the gray mater is at first devoid of any covering;
as it leaves the CNS, it acquires a covering
composed of the Schwann cells (neurolemma);
within this sheath of Schwann, the myelin sheath
is acquired by the larger peripheral nerves
• its substance is a lipid, glistening substance that
imparts the whitish color of the white mater; it is
limited peripherally by the interfascicular glia cells
(a type of oligodendroglia)
• it is dissolved after ordinary fixation methods
having a network of protein material called
neurokeratin, around the nerve fiber; it can be
fixed & stained black by osmium tetroxide
 TEM of a
Myelinated Axon
Nu = nucleus of an
Oligodendrocyte

TEM of an
Unmyelinated
Axons
Nu = nucleus of an
Oligodendrocyte
• EM: demonstrates the myelin as a series of concentric layers of
Schwann cell plasma membrane
• mature myelin shows regular lamination with concentric, regular,
dense laminar or period lines of 30Ǻ (3μm) separated by light
intervals of about 100Ǻ (10μm); finer dense lines of 20Ǻ (2μm)
thickness called the intraperiod lines, dissect the inner cytoplasmic
surfaces of the Schwann cell plasma membrane & intraperiod lines
by appositions of the outer surfaces (“jelly roll” hypothesis)
TEM of a
Myelin
Sheath
Myelination of Axons by Oligodendrocytes
Sheath of Schwann (Neurolemma)
• composed of sheath of flattened cells termed the
neurolemmal sheath or neurolemma, forms a thin
sleeve around the myelin, which in turn, surrounds
the axon
• after passing through the white mater, a nerve
fiber leaves the CNS & acquires a thin, distinct
nucleated sheath of Schwann; as the nerve leaves
the CNS, it carries with it the glia cells to form the
sheath of Schwann
• in embryonic life, Schwann cells accompany
outgrowing axons & migrate from branch to
branch until they form complete neurolemmal
sheaths; this thin membrane contain flattened
nuclei that are alternately arranged along the
segments of the nerve fiber; a small Golgi complex
& a few mitochondria can be seen in the
attenuated cytoplasm of these cells of Schwann
• EM: reveals that myelin is actually part of the
Schwann cell being closely applied to the axon,
surrounding it & making several encircling turns
around it; the concentric lamellae of the plasma
membrane of the Schwann cell is called the myelin
sheath; the most superficial lamellae containing
the nucleus is called the neurilemmal sheath or
the Schwann sheath proper
• they are ectodermal in origin & are essential to
the vitality & function of peripheral nerve fibers;
they form myelin but are also necessary for
regeneration of axons; after division, an axon is
regenerated from the central stump, i.e. from the
end continuous with the nerve cell body; it then
grows peripherally to its termination along a
channel formed by Schwann cells; after injury,
these cells can also become phagocytic, removing
cellular debris
• they are not present in the CNS; their function is performed by
oligodendrocytes (oligodendroglia), a type of neuroglia
• myelin contains about 80% lipid, including cholesterol,
phospholipids, glycolipids, & about 20% protein; the high lipid
content explains the whiteness of peripheral nerves (e.g. the white
rami of the autonomic nerves as compared with the gray rami that
contain primarily unmyelinated fibers), as well as the distinction
between white and gray mater of the CNS
Classification of Nerve Fibers:
- may be classified as myelinated or non-myelinated
I. According to their coverings, they may be classified into 4 types for
purposes of microscopic study:
a. Medullated nerve fiber with Neurolemma
b. Medullated nerve fiber without Neurolemma
c. Non-medullated nerve fiber with Neurolemma
d. Non-medullated nerve fiber without Neurolemma
A. Medullated nerve fiber with Neurolemma
• contains both coverings of myelin sheath &
neurolemma or nucleated sheath of Schwann, so
that they are considered the biggest among the
other varieties
• it is made up of a central core of neurofibrils which
are the continuation of the neurofibrils originating
from the cell body; these fibrils are embedded in a
small amount of neuroplasm, called the axoplasm;
the bundle of fibrils constitutes the axis cylinder
called axon at its origin from the cell body; these
fibrils are composed of finer & parallel
neurofilaments; a few, thin mitochondria,
microtubules & slender ER are present in the
axoplasm; covering this axis cylinder is a delicate
membrane called the axolemma of Kuhne
• the myelin sheath covers the axis cylinder; the thickness of the
sheath determines size of the nerve fibers; there are regular
annular deficiencies or constrictions along the course of the fiber
termed the Nodes of Ranvier – these are the places where the
branches or collaterals of the nerve fiber are given off at right
angles (EM); these are the places where the Schwann cells meet &
where nutritive substances easily gain entrance into the axis
cylinder
 TEM of a
Myelinated
Axons
Gaps = Nodes of
Ranvier
• the portion of the nerve fiber between 2
successive nodes of Ranvier is called internodal
segment which is longer when the nerve fiber is
thicker; its thickness is due to the increase of
myelin substance & the content of neurofibrils;
the segment appears shorter towards the end of a
nerve due to the diminution of neurofibrils; in the
region of the node, there are finger-like processes
of the neighboring cells of Schwann covering the
nodal area. The gap is important in the saltatory
transfer of action potential for stimulus
propagation along the nerve fiber
• Schmidt Lanterman’s Lines/Incisures of Schmidt –
several oblique & radially placed lines in the
myelin sheath within each internodal segment
(when stained with osmic acid); the portion
between 2 successive Schmidt incisures is called
myelin segment; on EM, these represents areas of
local separation of the spirally wrapped myelin
lamellae
• the myelin is covered externally by the nucleated
sheath of Schwann; this is a thin, nucleated
membrane whose nuclei appear alternately,
containing one for each internodal segment. At
the nodes of Ranvier, it dips & comes in contact
with the axis cylinder; this covering also
disappears like the myelin before the nerve fiber
ends so that all nerve endings are naked fibers
• there is a thin, delicate fibrous connective sheath outside
the neurolemma termed CT sheath of Key & Retzius or the
Sheath of Henle – this forms a part of the endoneurium
that carries the capillary blood vessels to the individual
nerve fibers
B. Medullated nerve fiber without Neurolemma
• found only in the white mater (CNS) corresponding to the
portions of axons & dendrons that traverse the white
mater after passing the gray mater
• it is composed of the axis cylinder surrounded by the
axolemma & which is covered by the myelin sheath
• the nodes of Ranvier are not prominent
• seen lying in rows between the myelinated fibers are the
interfascicular glia cells (oligodendrocytes), arranged in the
form of a membrane
 Bundles of nerve
fibers (BNF)
surrounded by an
Epineurium (Epn)

Perineurium (arrow)
surrounds each
bundle
 SEM of a nerve bundle

Ep = epineurium; Pe = perineurium; En = endoneurium;

Fa = fascicle; BV = blood vessel
 High mag of a nerve bundle

A (arrow) = fibroblast; B (arrow) = Schwann Cells

 TEM of myelinated (MS) nerve fibers

Sch = Schwann cell; Ax = axons; Un = unmyelinated axons

C. Non-medullated nerve fiber with Neurolemma
• it constitutes majority of the sympathetic nerves that are
sometimes termed Remak fibers
• it is composed of the axis cylinder with its axolemma &
covered by the thin neurolemma; these fibers are very thin
due to the absence of the myelin substance
• the nodes of Ranvier are not prominent
• the Schwann cell membrane envelops the fibers
• e.g. post-ganglionic fibers
D. Non-medullated nerve fiber without Neurolemma
• it is composed only of the axis cylinder not having acquired
any covering
• it is found in the cyto-proximal & cyto-distal portions of all
nerve fibers (portions of nerve processes arising directly
from the cell bodies located in the gray mater
**These 4 varieties of nerve fibers may be encountered in
the course of a single nerve fiber
II. According to diameter:
• in peripheral nerves, the fibers fall into 3 distinct groups:
a. Group A fibers – large fibers (1 – 22μm in dia.) that conduct at 15 – 100
m/sec; they include motor & sensory fibers
b. Group B fibers – fibers (1 – 3μm in dia.) that conduct at 3 – 14 m/sec &
include mainly visceral sensory fibers
c. Group C fibers – small unmyelinated fibers (0.3 – 1.3μm in dia.) conducting
at 0.5 – 2 m/sec carrying autonomic & some sensory impulses
III. According to presence or absence of myelin:
a. Motor nerve fibers – are thick & heavily myelinated
(skeletal muscles)
b. Visceral smooth muscle – are thin, lightly myelinated or
without myelin
c. Tactile fibers – are medium-sized & moderately
myelinated
d. Pain & Taste fibers – are thinner with less myelin or
none at all
e. Olfactory nerve filaments – are always unmyelinated
IV. According to function:
a. Afferent (incoming) pathway
e.g. spinothalamic; spino-cerebellar
b. Efferent (outgoing) pathway
e.g. cortico-bulbar; cortico-spinal
V. According to Pharmacological differences of
component fibers (autonomic nerves):
a. Sympathetic/adrenergic – stimulation leads to the
liberation of the substance norepinephrine
b. Parasympathetic/cholinergic – stimulation leads to
liberation of a substance, acetylcholine
Cerebrospinal nerves
• constitute the cranial & spinal nerves which are
composed of medullated or myelinated fibers with
neurolemma
• they are continuation of axons or dendrons that
have gone outside of the brain & spinal cord
Autonomic Nerves (Sympathetic & Parasympathetic nerves):
Sympathetic nerves – are composed of preganglionic myelinated
fibers & postganglionic unmyelinated fibers; the preganglionic
fibers come from the spinal cord to enter a peripheral ganglion;
while the postganglionic fibers arise from the nerve cells within the
ganglia to proceed to some organs as the non-medullated nerve
fibers with neurolemma (Remak fibers)
Parasympathetic nerves – are composed of long preganglionic
myelinated fibers coming from the brain & sacral portion of the
spinal cord to end in some terminal ganglia or within the wall of the
organ innervated; the postganglionic fibers are very short &
unmyelinated; the portions of the central & peripheral NS primarily
concerned with the regulation of visceral activities are often
collectively termed the visceral, or ANS in contrast to somatic or
cerebrospinal
The higher brain centers regulate both somatic &
visceral functions; through most neural levels,
there is an intermingling & association of visceral
& somatic neurons. Peripherally, visceral motor
fibers are found in all the spinal nerves & in cranial
nerves III, VII, IX, & X.
Interposed in the efferent peripheral pathway
between the CNS & visceral structures are
aggregations of nerve cells termed the autonomic
ganglia – they send out axons to terminate in the
visceral effectors, smooth muscle, heart muscle, &
glandular epithelium
Peripheral Nerve Endings
each peripheral nerve fiber (sensory, motor, or
secretory) will later end in some periphery organ
with one or several terminal arborizations
(telodendrion); some will ramify as free endings in
the non-nervous tissue cells by means of
specialized terminations; fibers ending in sensory
receptors are dendrites, while those with motor or
secretory endings are axons; the terminations are
called axon endings (the structure is adopted to
increase the surface contact between the neuron
& its related non-nervous element
nerve endings are found in almost all tissues,
except in cartilage, mucous tissue, enamel of
teeth, & in the calcareous matrix of bones; the
axon endings convey nerve impulses; the efferent
fibers terminate in tissues in which they excite
activity by releasing a neurotransmitter; in some
somatic effector (skeletal muscle), the transmitter
released is acetylcholine
in afferent fibers, the receptor portions are
located throughout the body where nerve fibers
end freely in the tissues or in arborizations of the
afferent fibers; they may terminate freely among
the body tissues or they are surrounded by special
CT capsules; distinction: free, non-encapsulated, &
encapsulated
Receptor Endings
• special sensory nerve endings or receptors that
are classified into 5 basic functional types:
a. Mechanoreceptors – respond to mechanical
deformation
b. Thermoreceptors – respond to changes in temperature
(cold/heat)
c. Nociceptors – respond to any stimulus that bring about
damage to the tissues
d. Electromagnetic receptors – sensitive to changes in
light intensity & wavelength (rods & cones)
e. Chemoreceptors – respond to chemical changes
associated with taste & smell, and O2 & CO2
concentration in the blood
Anatomic Types of Receptors
• sensory endings can be classified into non-
encapsulated & encapsulated receptors
A. Non-encapsulated Receptors
a. Free Nerve Endings
widely distributed throughout the body; found
between the epithelial cells of the epidermis
(penetrating up to the granular skin layer), the
cornea & the alimentary tract, & in the CTs; it may
also include the dermis, fascia, ligaments, joint
capsules, tendons, periosteum, perichondrium,
Haversian system of bones, tympanic membrane,
dental pulp & muscles
 its afferent nerve fibers are of small diameter & are either
myelinated or nonmyelinated; its terminal endings are
devoid of myelin sheath & these have no Schwann cells
covering their tips
 most of these endings detect pain, while others detect
crude touch, pressure & tickle sensations, and possibly
cold & heat
b. Merkel’s Discs
 found in hairless skin & in hair follicles
 its nerve fibers passes into the epidermis & terminates as a
disc-shaped expansion that is applied closely to a dark-
staining epithelial cell in the deeper part of the epidermis
called the Merkel cell
 in hairy skin, clusters of Merkel discs, known as tactile
domes are found in the epidermis between the hair
follicles
 are slowly adapting touch receptors that transmit
information about the degree of pressure exerted on the
skin
c. Hair Follicle Receptors
its nerve fibers wind around the follicle in its outer
CT sheath below the sebaceous gland; some
branches surround the follicle, while others run
parallel to its long axis; many naked axon filaments
terminate among the cells of the outer root
sheath
bending of the hair stimulates the follicle receptor,
which belong to the rapidly adapting group of
mechanoreceptors; it remains silent while the hair
remains bent, but when the hair is released, a
burst of nerve impulse is initiated
B. Encapsulated Receptors
• show wide variations in size & shape, and the termination
of the nerve is covered by a capsule
a. Meissner’s Corpuscles
 are located in the dermal papillae of the skin (palm of the
hand, sole of the foot, skin of the nipple, & external
genitalia)
 each is ovoid in shape & consists of a stack of modified
flattened Schwann cells arranged transversely across the
long axis of the corpuscle
 it is enclosed by a capsule of CT that is continuous with the
endoneurium of the nerves that enter it; a few myelinated
nerve fibers enter the deep end of the corpuscle;
myelinated & unmyelinated branches decrease in size &
ramify among the Schwann cells
 are very sensitive to touch & are rapidly adapting
mechanoreceptors; receptors stimulated during 2-point
tactile discrimination
Meissner’s Corpuscle
Meissner’s Corpuscle within a dermal papilla
Meissner’s Corpuscle
b. Pacinian Corpuscles (Lamellar or Vater-Pacini
Corpuscles)
 widely distributed throughout the body;
abundant in the dermis, subcutaneous, ligaments,
joint capsules, pleura, peritoneum, nipples, &
external genitalia
each is ovoid measuring about 2mm long & about
100 – 500μm acres
it consists of a capsule & a central core containing
the nerve ending; the capsule consists of
numerous concentric lamellae of flattened cells
on section, it resembles a sliced onion; between
the adjacent lamellae are amorphous material &
collagen fibers
Pacinian with a core nerve fiber and concentric flatten modified
Schwann cells
TEM of a Pacinian Corpuscle
 a large myelinated nerve fiber enters the corpuscle & loses
its myelin sheath and then its Schwann cell covering; the
naked axon, surrounded by lamellae formed of flattened
cells, passes through the center of the core & terminates in
an expanded end
 are rapidly adapting mechanoreceptors that are sensitive
to deformation & therefore respond to pressure or
tension; sensitive to vibration (respond up to 600
stimuli/sec)
c. Golgi Mazzoni Corpuscles
 resembles the Pacinian corpuscles except that their
lamellated capsule is thinner; the granular core of
protoplasm is more abundant; are smaller in size
 its nerve fiber enters in a similar manner as in the Pacinian
corpuscle; the single myelinated fiber forms a rich
arborization with varicosities
 its function is also for mediating deep pressure
d. End-Bulb of Krause (Bulbous Corpuscles of Krause)
 are found in the conjunctiva, lips, mucous membranes of
the tongue, cheeks, soft palate, epiglottis, nasal cavities,
lower end of rectum, peritoneum, serous membrane,
tendons, ligaments, CT of nerve trunks, synovial
membranes of certain joints & the external genitalia (glans
penis & clitoris – genital corpuscles)
 are spheroidal & measures about 50 μm in dia.; some may
be compound & contain capsule that is continuous with
the endoneurium
 a single myelinated nerve fiber on entering the corpuscle
loses its myelin; covered by its Schwann cells, the nerve
fiber then branches becomes coiled, or runs a straight
course to terminate in an expanded end
 its precise function is unknown
e. Ruffini’s Corpuscle (Terminal Cylinder)
 are found in subcutaneous tissue of the finger tips & in joint
capsules
 elongated bodies of considerable size composed of a core of
granular protoplasm whose very thin cellular capsule encloses
several bundles of CT fibers & an apparent fluid space
 are slowly adapting mechanoreceptors (stretch receptors), which
respond when the skin is stretched
Functions of Cutaneous Receptors:
• although the body has different receptors, all
nerves only transmit nerve impulses
• the type of sensation felt is determined by the
specific area of the CNS to which the afferent
nerve fiber passes
e.g. heat/cold/touch/pressure  (+) pain
fibers  “pain”
• 3 groups of nerve terminations can be
distinguished:
1. Endings in the Epithelium
2. Endings in Connective tissue
3. Endings in Muscle
1. Nerve Endings in Epithelium
 terminations in the epithelial layers of the skin & mucous
membranes are probably only sensory & those in the epithelial
glands partly secretory, partly sensory
 free sensory epithelial endings are abundant where sensitivity is
highly developed: in the epithelium of the cornea, mucous
membrane of the respiratory passages & oral cavity, & in the skin
2. Nerve Endings in Connective Tissue
are numerous & of many forms particularly in the
dermis & mesothelium of the mucous & serous
membranes, around the joints, in the
endocardium
are either free or encapsulated endings
more complex endings are found in the skin &
hypodermis, mucous & serous membranes,
endocardium, cornea, sclera, & periosteum
non-encapsulated endings are frequent in the
papillary layer of the skin, CT of mucous
membranes; pericardium & endocardium; the
terminal branches form spherical or elongated
structures resembling glomeruli
3. Nerve Ending in Muscle
a. Smooth & Cardiac Muscle
 thin, unmyelinated nerve fibers separate from complicated
plexuses & eventually contact or approach the surface of
the muscle cells
 Visceral sensory fibers ramify in the CT between smooth
muscle bundles or contact the muscle fibers themselves. In
Cardiac muscle, the tissue is permeated by thin fiber
passing between the muscle trabeculae that appear to end
near the surface of the muscle fibers without forming
specialized contacts with them
 Visceral motor axons give rise to terminal branches that
carry numerous boutons en passant (boutons
terminaux/end feet of Held/neuropodia) filled with
synaptic vesicles; these endings remain at a variable
distance from the surface of the smooth & cardiac muscle
cells; they do not form specialized junctions with their
membrane
b. Motor Nerve Endings (Somatic efferent) in Striated
Muscle
 the motor end plate (myoneural junction) represents the
termination of somatic motor nerve
 each motor nerve fiber branches to supply many muscle
fibers; the motor neuron together with the muscle fibers
that it innervates is termed as “motor unit”; the finer
muscles that are concerned with precise movement have
an abundant nerve supply
 the somatic efferent fibers terminate upon the skeletal
muscle fibers in small, flattened oval expansions; this
specialized junctional region at the termination of a motor
nerve on skeletal muscle fibers is termed the motor end
plate/myoneural junction; they are located in narrow zones
in a given muscle; each end plate always lie in mid-portion
of the fiber it supplies; larger muscle fibers have larger end
plates
a single motor nerve fiber provides end plates to a
variable number of the large extrafusal muscle
fibers
the myoneural junction is recognized as a slight
elevation on the muscle fiber marked by a local
accumulation of nuclei; there are 2
morphologically distinguished types:
1. “Arborization nuclei” – type of nuclei of the motor end
plate belong to the terminal Schwann cells or sheath
cells associated with motor nerve endings; collectively
referred to as “teloglia”
2. “Fundamental/sole nuclei” – usually larger & less
intensely stained; they are nuclei of the underlying
muscle fibers that converge in the region of the motor
end plate
 with metallic staining, the axis cylinder of the motor nerve, after
losing its myelin sheath, forms a terminal arborization among the
nuclei clustered at the junction
 the termination of the axis cylinder occupy recesses in the surface
of muscle fiber called synaptic trough (synaptic gutter/primary
synaptic cleft); the surface of the underlying muscle into the
underlying sarcoplasm; this specialization of the surface of the
muscle fiber is called the subneural apparatus
EM: the teloglial cells never penetrate into the
synaptic cleft although they cover the outer
surface of the axon terminal
: the lamellae of the subneural apparatus are
narrow
: secondary synaptic clefts are formed by infolding
of the sarcolemma lining the primary synaptic
trough
: presence of a glycoprotein (gap substance)
boundary layer that separates the axolemma &
the sarcolemma
: the axon terminals do not penetrate the
sarcolemma & do not intermingle with the
constituents of the muscle fiber
its axoplasm contains mitochondria & a very large
number of 400 – 600Ǻ small vesicles (site of
storage of acetylcholine); there is also abundance
of mitochondria in the subneural sarcoplasm; the
subneural apparatus of the motor end plate is
involved in acetylcholinesterase activity localized
in or near the sarcolemma lining the secondary
cleft
c. Sensory Nerve Endings in Striated Muscle
(Neuromuscular Spindles)
Neuromuscular spindles – are found in skeletal
muscles; most numerous toward the tendinous
insertion of the muscle
they provide sensory information used by the CNS
in the control of muscle activity
the whole structure functions as a unit in reflex
regulation of muscle tone
it is innervated by both motor & sensory nerves
each spindle measures about 1 – 4 mm in length &
surrounded by a fusiform capsule of CT; within the
capsule are 6 – 14 slender intrafusal muscle fibers
(ordinary muscle fibers situated outside the
spindles are referred to as extrafusal fibers)
there are 2 types of intrafusal fibers:
1. nuclear bag fibers
2. nuclear chain fibers
 *Nuclear bag fibers – with numerous nuclei in the equatorial region
which is expanded; cross striations are absent
- larger in diameter & they extend beyond the capsule at each end
to attack the endomysium of the extrafusal fibers
*Nuclear chain fibers – nuclei form a single longitudinal row in the
center of each fiber at the equatorial region
 2 types of sensory innervation:
1. annulospiral endings
2. flower spray endings
*Annulospiral endings – are situated at the
equator of the intrafusal fibers; as the large
myelinated fiber pierces the capsule, it loses its
myelin sheath & the naked axon winds spirally
around the nuclear bag or chain portions of the
intrafusal fibers
*Flower spray endings – mainly situated on the
nuclear chain fibers some distance from the
equatorial region; a myelinated nerve fiber slightly
smaller than that of the annulospiral ending
pierces the capsule & loses its myelin sheath; the
naked axon branches terminally & ends as
varicosities
 stretching of intrafusal fibers results in stimulation of the
annulospiral & flower spray endings; nerve impulses pass to the
spinal cord in the afferent neuron  (+) large alpha motor neurons
(anterior gray horn)  (+) extrafusal fibers = muscle contracts
 the neuromuscular spindle plays a vital role in controlling the
activities of voluntary muscles
 Neurotendinous Spindles
are most numerous near the junctions of tendons
with muscles
they provide the CNS with information concerning
tension within a tendon & are therefore,
associated with the control of muscle tone
it resembles the muscle spindle except that
collagenous tendon fibers, termed the intrafusal
tendon fibers, replace the intrafusal muscle fibers
of the muscle spindle
each spindle consists of a fibrous capsule that
contains a small bundle of loosely arranged
tendon fibers
 the tendon cells are larger & more numerous than elsewhere in the
tendon; one or more myelinated sensory nerve fibers pierce the
capsule, lose their myelin sheaths, branch freely, & terminate in
club-shaped endings
 stretching of the tendon results in deformation of the nerve
endings by the adjacent tendon fibers within the spindle
 Golgi tendon organs – are also stretch receptors & like muscle
spindles, are concerned with proprioception
Nerve Trunk
it is made up of several fasciculi or bundles of
nerve fibers that is covered externally by a
relatively strong dense CT called the epineurium –
it is composed of fibroblasts & collagenous fibers
oriented mainly in a longitudinal manner
containing blood vessels; the covering gives off
several trabeculae or septa, the perineurium that
surrounds the bigger bundles of nerve fibers; in
turn, it sends finer trabeculae that surrounds
smaller bundles & ultimately, individual nerve
fibers; this constitutes the endoneurium in which
the sheath of Henle or Key-Retzius is a part or
continuation
 the endoneurium is composed of delicate collagenous &
reticular fibers, amorphous ground substance & flattened
fibroblasts; it is closely adherent to the neurolemma &
thus, is difficult to distinguish from each other
 blood supply: numerous branches from adjacent arteries
enter the epineurium, anastomose freely & run mainly
longitudinally
: smaller vessels extend into the perineurium
: extensive capillary network in the endoneurium
: blood supply is carried to the individual nerve fibers
located in the central portion of the nerve trunk
: vessels supplying the nerves are termed Vasa nervorum
: vessels supplying the nerve fibers within the fibrous
covering & septa are called nervi nervorum
Synapse
it is termed on the basis of position:
a. Axo-dendritic – from axon to dendrite
b. Axo-somatic – from axon to perikaryon or soma
c. Axo-axonic – from axon to axon (rare)
it is defined as a specialized membranous contact
between nerve cells or between nerve cells &
effector organs (muscle & gland cells)
physiologically, it is the site of transneuronal
transmission of an impulse; in few instances, the
electrical signal may be passed directly to the
adjacent cell by a gap junction or nexus (epithelia,
smooth muscle, & intercalated discs of heart
muscle) – electrical synapses
more commonly, the impulse is transmitted from
cell to cell by a chemical mediator or
neurotransmitter substance
the number of synapses in a neuron varies
enormously; a motor neuron may have as many as
1,800 synapses; granule cells of the cerebellum
may have only a few; a Purkinje cell of the
cerebellum may have several hundred thousand
endings upon its dendrites alone
the forms of synaptic endings vary; there are
usually tiny swellings along the course of axons
(synapses en passant) or at the tips of axonal
branches (boutons terminaux); others may give
rise to terminal twigs that form “bouquets” or
loose “baskets” adhering to the body or dendrites
of another nerve cell
 basically, it is formed by:
1. the expanded termination of an axon called the pre-synaptic terminal or
element
2. the post-synaptic element – or area of the cell contacted
3. the synaptic cleft – intervening space of 20 – 30 nm width
Pre-synaptic terminal
 it is expanded into a small bulb or bouton terminal (end foot), but
similar expansions occur along the course of an axon (bouton en
passage) so that a single axon may make synapses with many
different neurons
EM: may contain numerous mitochondria &
abundant small vesicles of 40 – 60μm in dia. which
contain the transmitter substance; these vesicles
vary in content, some containing clear material
while others contain a dense core; synapses that
releases the neurotransmitter acetylcholine
(cholinergic synapses) contain clear vesicles, while
terminals that release noradrenalin (adrenergic
synapses) contain dense-core vesicles
its membrane (plasmalemma), is thickened by the
presence of electron-dense particles projecting
into the pre-synaptic terminal & connected by fine
filaments with an associated network of actin-like
filaments in the adjacent cytoplasm
Synaptic Cleft
the pre- & post-synaptic membranes are closely
apposed, separated by a space about 20 – 30μm
there is some electron-dense filamentous material
that appears to be associated with the outer
surfaces of both pre- & post-synaptic membranes,
probably related to cell coat material (glycocalyx)
& that appears to hold the 2 membranes firmly
together
passage of a transmitter substance across the cleft
is involved in the transmission of activity from one
neuron to another or to an effector; in addition to
acetylcholine & noradrenalin, other transmitters
such as gamma-amino butyric acid (GABA),
dopamine, & serotonin have been identified;
 after their release, all combine with receptor sites on the post-
synaptic membrane & affect membrane permeability to certain
ions, either to generate an action potential (excitatory) or to inhibit
(inhibiting synapses)
Post-synaptic Element
 its membrane is more dense than the pre-synaptic membrane due
to the presence on its cytoplasmic side of dense granular material
called the subsynaptic or post-synaptic web (helps to maintain
cohesion of the synapsing cells)
Receptors
a. Baroreceptors (presso-receptors) – these are mechanoreceptors
present in the walls of large arteries; respond to pressure or
tension as the vascular walls become distended during an elevation
of BP
- it consists of a free, spray-type nerve ending in the adventitia of
all large arteries in the neck & thorax; they are abundant in the
aortic wall & the carotid sinus, the dilatation of the common
carotid artery near its bifurcation
- they regulate the ABP
b. Chemoreceptors – are transducers, sensitive to
chemical substance converting chemical stimuli to
nerve impulses; the olfactory epithelium of the
nose & the taste buds of the tongue
- aortic & carotid bodies, & glomus pulmonale
(sensitive to changes in concentration of blood 02,
CO2, & H⁺ ions
*carotid bodies – located at the bifurcation of the
common carotid artery
*aortic body – lies between the arch of the aorta
& the pulmonary artery
*glomus pulmonale – situated in the wall of the
pulmonary arteries near the root of the lungs;
they are round or oval bodies, 2 – 3 mm in dia.
consisting of densely arranged glomus cells, some
autonomic ganglion cells & denuded nerve fibers
 Neuroglia
• this is the supporting tissue of the CNS (brain &
spinal cord), including the olfactory nerves, optic
chiasm, & retina; fine septa of areolar CT from the
pia mater penetrate into the CNS carrying the
blood vessels
• they dominate the neurons in microscopic
sections of the nervous tissue; are non-excitable &
do not conduct nerve impulses
• the supporting cells are characterized by their
generally small size & their large numbers
• they are not seen well in ordinary preparations for
their processes are not visible
• on H&E: only the nuclei are visible; identification
of neuroglial cells is dependent upon the size &
shape of nuclei, & the arrangement of chromatin
granules within them
• they function to bind together the nervous tissue
proper
• the term “neuroglia” is applied to:
1. Ependymal cells
2. Astrocytes or astroglia* (fibrous or protoplasmic
astrocytes)
3. Oligodendrocytes or oligodendroglia*
(perineuronal/interfascicular/perivascular
oligodendrocytes)
*collectively called macroglia which are ectodermal in
origin
4. Microglia (mesoglia) – from mesodermal cells of the
pia mater that carry blood vessel into the CNS
Glial Cells
of the CNS
Ependyma
 the entire CNS develops as a hollow cylinder (neuron tube)
 cavities remain in the adult as the ventricles of the brain & the
central canal of the spinal cord; its linings is made up of the
Ependyma which retains the epithelial character present in the
early embryo
 the embryonic ependyma is ciliated; in some parts, the cilia may
persist into adult life & appear to be of cuboidal type
Ependymal Cells lining spaces in the CNS
in mature brain, the broad bases of ependymal
cells taper to long thread like processes that
branch. In the ventral fissure of the spinal cord,
some ependymal cells span the entire distance
between ventricular & external surfaces; they
form a dense internal limiting membrane at the
ventricular end; at the external surface, under the
pia mater, the ependymal threads expand into
pedicles that fuse into a thin, smooth dense
membrane, the external limiting membrane of the
CNS
EM: have numerous microvilli; cytoplasm contains
fibrils which may extend into basal cytoplasmic
processes; desmosomes & junctional complexes
are present
SEM of Ciliated (Ci) Ependymal Cells
Astrocytes
are star-shaped cells with numerous branching
processes
its nuclei is large, dark-staining & the cytoplasm is
granular
are the biggest among the glia cells
2 types by the character of their cytoplasmic
processes:
a. Protoplasmic astrocyte/Mossy cell/Short-rayed
astrocytes
- they have numerous processes that are short,
wavy or tortuous giving off several short branches
- the cytoplasm within its processes are granular;
along the processes, the granules produce several
spheroidal swellings called gliosomes
 - one or more processes may have terminal
expansions which contact blood vessels called
perivascular foot/sucker foot – they plug the pores
of the endothelium of the brain capillaries serving
as a BBB
- they are found mainly within the gray mater of
the brain & spinal cord, often closely adjacent to
the neuron cell bodies (as a type of satellite cell)
b. Fibrous astrocytes/Spider cell/Long-rayed
astrocytes
- have fewer processes that appear longer & more
or less straight with fewer branches
- embedded within its cytoplasm are fibrillar
structures; gliosomes & perivascular feet are also
present
- it is more numerous in the white mater
Astrocytes (arrows) supporting a capillary
 - are the scarring cells of the nervous system filling
in gaps after tissue is lost in various disease
processes
- 2 modified types:
1. Muller cell of the retina – elongated columns of
cells extending across the thickness of the neural
retina; they have expanded foot processes which
form the inner & outer limiting membranes of the
retina
2. Bergmann glial cell of the cerebellum
c. Mixed/Plasmatofibrous
- astrocytes found at the boundary between gray
& white mater
- their processes entering the gray mater have a
protoplasmic character while those entering the
white mater are fibrous
Astrocytes
Fluorescent stained Astrocyte
Oligodendroglia
are smaller cells with dark-staining nucleus & a
scanty cytoplasm with very few short processes
having few branched processes (“oligo” – few or
scanty)
subdivided into (according to location):
a. perineuronal satellite – found surrounding the
nerve cells in the gray mater of the CNS
b. perivascular satellite – their cell bodies &
processes are attached intimately to the walls of
blood vessels
c. interfascicular glia or sheath cells – they relate
intimately to nerve fibers (myelinated without
neurolemma) along which they form rows or
columns in the white mater of the CNS
 its cells are considered the homologue of the neurilemmal
cells of Schwann
 its cytoplasm is electron-dense & consists mainly of
mitochondria & microtubules; these characteristics permit
their identification in EM (nuclei are round, small & dense)
 in tissue culture: they show intense movements
characterized by rhythmic pulsation
Microglia/Mesoglia
 are small cells with small but deeply stained nucleus
surrounded by scanty cytoplasm
 has few extensions that are short & twisted covered with
numerous tiny pointed twigs or “spines”
 are scattered everywhere throughout the brain & spinal
cord
 are capable of amoeboid movement & phagocytosis
(considered as macrophages of the CNS)
SEM of a Microglial Cell (arrow) in a Brain
Ventricle
Neuroglia
• they do not form a syncitium
• may play an essential role in the communication function of the
nervous system
• also an important mediator for normal metabolism of neurons
• are actively involved in degeneration & regeneration of the nerve
fibers, in vascular disorders, & in various infectious diseases
• are chief source of tumors of the CNS
 Gray & White Mater
Gray mater
• the CNS is composed of gray mater & white mater
• the gray mater is composed of 3 elements:
a. Nerve cell bodies – arranged in columns in the spinal
cord or in layers as in the brain or as just masses of
nerve cells as in the different nuclei of the brain (basal
ganglia)
b. Proximal portions of the nerve processes, the axons &
dendrons
c. Neuroglia – the glia cells in the gray mater are mostly
the protoplasmic variety; glia fibers form a meshwork;
delicate strands of areolar tissue carrying the small
blood vessels are found
• it appears dark in color due to the absence of
myelin & the presence of nerve cell bodies
White mater
• it does not contain nerve cell bodies but only
fibers, which may be myelinated or non-
myelinated, and neuroglia with a small amount of
areolar CT containing blood vessels
• due to the glistening whitish appearance of
myelin, the white mater attains its whitish color
• the nerve fibers are arranged in parallel bundles
called fiber tracts that course up & down the
spinal cord; in the neurological supporting tissue,
the interfascicular glia cells align themselves,
forming a sheath along the myelinated fibers; the
fibrous astrocytes are abundant in the white
mater
• it is composed of:
a. medullated or myelinated – nerve fibers with a few non-myelinated ones
b. neuroglia with delicate strands of areolar tissue containing small blood
vessels; found abundant in the white mater are the fibrous variety of
astrocytes
• the masses of gray mater found embedded in certain areas of white
mater are called nuclei or ganglia
• localization of gray mater & white mater varies according to the
area & the organization of the nervous tissue considered
Spinal Cord
• it is roughly cylindrical in shape & composed of an
inner core of gray mater surrounded by an outer
covering of white mater
• Gray mater is seen on cross section as an H-
shaped structure with an anterior & posterior gray
columns/horns, united by a thin gray commissure
containing the small central canal
- the nerve cells are multipolar & the neuroglia
forms an intricate network around the nerve cell
bodies; in the anterior gray columns, the majority
of the nerve cells are large & their axons pass out
in the anterior roots of the spinal nerves to
innervate skeletal muscles
Spinal cord – inner gray matter and outer white
Spinal cord - inner gray matter (G) w/ cell bodies
and outer white matter (W) of axons and myelin

W
• White mater consists of nerve fibers, neuroglia & blood vessels; it
surrounds the gray mater & its white color is caused by the high
proportion of myelinated nerve fibers
Cerebellum
• Gray mater is located in the surface as a thin cortex overlying the
centrally placed white mater; there are also small collections of
nerve cell (nuclei) in the central parts of the cerebellum (nucleus
dentatus, emboliformis, globosi, & fastigii)
Low mag of the
Cerebellum or
Cerebellar
Cortex
(arrow)
Structure:
• the cerebellar cortex is uniform in all parts of the
cerebellum
• it has 3 layers (from the surface proceeding inwards):
1. Outer molecular layer – relatively few cells & few
myelinated fibers
- the superficial cells are stellate in shape with short, thin
dendrites & fine myelinated axons that run horizontally
- the large, deeper stellate cells situated in the vicinity of
the Purkinje cell bodies also are known as “basket cells”;
many of their numerous branching dendrites ascend to the
surface & the axons run parallel to the sagittal plane
ending in relation or around the bodies of the Purkinje
cells; a narrow horizontal plexus of myelinated fibers
composed of collaterals from the axons of Purkinje cell is
found only in its deepest portion
Cerebellum or Cerebellar Cortex
2. Middle Ganglionic layer – consists of a single row of large, flask-
shaped bodies with 2 processes (Purkinje cell); each cell gives off 2
or 3 main dendrites which enters the molecular layer forming a fan-
shaped dendritic arborization extending to the surface; the axon
rises from the part of the cell opposite the dendrites, acquires a
myelin sheath, passes through the granular layer & enters the
underlying white myelin to go to one of the deep cerebellar nuclei
or to some other parts of the cortex
High mag of the Purkinje Cells of the Cerebellum
The Dendritic Tree of Purkinje Cells
Cajal’s drawing of
Purkinje Cells
3. Granular layer – in ordinary stains, presents the
appearance of closely packed chromatic nuclei
resembling lymphocytes; irregular light spaces
constitute the so-called “islands” or “glomeruli”;
the granule cells are small, multipolar with short 3
or 4 dendrites which arborized in peculiar claw-
like endings; the unmyelinated axons ascend to
the molecular & run transversely to the dendritic
expansion of the Purkinje cells
- scattered throughout the layer are the Golgi type
II cells or cells of Gehucten which have vesicular
nuclei & chromophilic bodies; their branching
dendrites enter the molecular layer, while their
terminal fibrils come in contact with the dendritic
terminals of the terminals of the granule cell
• it has the terminations of the mossy & climbing
fibers passing into the cerebellar cortex from the
white mater of the brain stem & spinal cord; the
mossy fibers are thick & synapse in cells of the
granular layer, while climbing fibers pass through
the granular layer to terminate on Purkinje cells
Cerebral Cortex
• Gray mater is located on the surface as cerebral
cortex
• White mater underneath the gray cortex
(medullary substance) is composed of bundles of
myelinated fibers passing in all directions; these
fibers are supported by neuroglia & are
functionally composed of 3 main groups:
association fibers, projection fibers, &
commissural fibers
The Cerebral Hemispheres
• a striking feature of cortical structure is its
lamination; in sections stained by Nissl method,
cell bodies are not uniformly distributed, but are
arranged in superimposed horizontal layers
• proceeding from the surface of the cortex towards
the white or medullary substance, these layers
include:
I. Molecule/plexiform layer
it contains relatively few cells of 2 types:
a. cells with horizontal axons (horizontal cells of Cajal)
b. Golgi type II cells
within this are found the terminal dendritic
ramifications of the pyramidal & fusiform cells
from the deeper layers & the axonal endings of
the cells of Martinotti
 Cerebrum or Cerebral Cortex
M – molecular; G - granular; P – pyramidal layers

M
G
P
II. External Granular layer
consists of numerous closely packed small cells of
triangular or pyramidal shape whose apical
dendrites terminate in the molecular layer; their
axons descend to the deepest cortical layers where
many terminate; some enter the white mater as
association fibers
III. External Pyramidal layer
composed of typical well-formed pyramidal
neurons
there are 2 sublayers:
a. superficial layer of medium-sized pyramids
b. deeper layer of large ones
their apical dendrites go to the first layer, while
most of their axons enter the white mater as
association or commissural fibers
in the most superficial part of the layer, there are a
great number of horizontal myelinated fibers
constituting the band of Kaes-Bechterew
IV. Internal Granular layer
composed chiefly of closely packed stellate cells;
these are very small with short axons ramifying
within the layer; other larger cells have
descending axons terminating in deeper layers, or
may enter the white substance
the whole layer is permeated by a dense
horizontal plexus of myelinated fibers forming
external band Baillarger, which are considered to
be mainly the terminal ramifications of the
thalamo-cortical fibers
V. Internal Pyramidal/Ganglion layer
 consists principally of medium-sized & large pyramidal neurons
(Giant pyramidal cells of Betz), which constitutes the origin of the
pyramidal tract – the corticospinal & corticobulbar tracts
 they are intermingled with granule cells & the cells of Martinotti
 their axons enter the white mater chiefly as projection fibers; the
rich horizontal fiber plexus in the deeper portion of this layer
constitutes the internal band of Baillarger
VI. Multiform/Fusiform cell layer
 contains predominantly spindle-shaped cells whose long axis are
perpendicular to the cortical surface; it contains also granule,
Martinotti, & stellate cells
 it may be subdivided into:
a. an upper sublayer of more densely packed, larger cells
b. a lower sublayer in which the smaller cells are loosely arranged
 the whole layer is pervaded by fiber bundles that enter or leave the
medullary substance
Cortical Cells & Fibers:
• the principal types of cells found in the cerebral
cortex are:
1. Pyramidal cells – the most characteristic of the
cortex, having the form of a pyramidal or triangle
whose upper pointed end is continued toward the
brain surface as the apical dendrite
- there are also a number of more or less
horizontally running basal dendrites that spring
from the cell body & arborize in the vicinity of the
cell; the axon emerges from the base of the cell &
descends towards the medullary substance to
enter the white mater as a projection or
association fiber
Pyramidal Cells of the Cerebral Cortex
Silver stained Pyramidal Cells of the Cerebral Cortex
Cajal Pyramidal Cell Drawing (circa 1900) and replica
 - they contain a large vesicular nucleus with prominent
Nissl bodies; they are classified usually as small, medium,
and large neurons
- the giant pyramidal cells of Betz may be more than 100
micra in height & are found in the motor area of the pre-
central gyrus
2. Stellate/Granule cells – are small with a polygonal or
triangle shape
- have dark-staining nuclei & scanty cytoplasm, varying in
size from 4 – 8 micra
- these cells have a number of dendrites passing in all
directions, and a short axon that ramifies close to the cell
body
- some resemble pyramidal cells in that they have no apical
dendrite that extends to the surface, these are known as
stellate, pyramidal cells or star pyramids
- they are found throughout all layers of the cortex but are
especially numerous in layer IV
3. Spindle/Fusiform cells – found mainly in the
deepest layer, with their long axis usually vertical
to the surface
4. Horizontal cells of Cajal – small fusiform or pear-
shaped cells found in the most superficial layer;
their long axons run horizontally & arborize within
the layer
5. Cells of Martinotti – are small, triangular or
polygonal cells where axons are directed toward
the surface
- they are present in practically all cell layers &
extend variable distance; some arborize in the
same layer, while others send collateral to a
number of layers
• fibers in the cerebral cortex are disposed radially &
tangentially; they include the axons of pyramidal,
fusiform & stellate cells which leave the cortex as
projection or association fibers and the entering
afferent projection & association fibers
terminating within the cortex; ascending axons of
the cells of Martinotti, likewise, have a vertical
course
• the tangential fibers, running horizontal to the
surface, are composed principally of the terminal
branches of the afferent projection & association
fibers, the axons of the horizontal & granule cells,
& the terminal branches of collaterals from the
pyramidal & fusiform cells
 Meninges

• membranes of CT that protects the CNS (skull & vertebral column)

• 3 membranes that envelope the brain & spinal cord (from
outermost):
1. Dura mater – pachymeninx
2. Arachnoid*
3. Pia mater*
*the arachnoid & pia mater are closely adherent & often considered
as a single membrane called pia-arachnoid/leptomeninx
Diagram of the Meninges
Dura mater
• is the external meninx made up of dense fibrous CT continuous
with the periosteum of the skull bones
• it envelopes the spinal cord & is separated from the periosteum by
the wide epidural space containing thin-walled veins (epidermal
venous plexus), loose CT and fat; the dura mater is firmly
connected to the spinal cord on each side by denticulate ligaments;
the inner surface of the spinal dura is lined with squamous cells
• the cranial dura consists of 2 layers:
1. Endosteal layer – an outer layer of dense CT containing
numerous blood vessels & nerves; it is in direct contact
with the inner surface of bone & is, simply, the
periosteum on the inner surface of the cranial bones
2. Fibrous layer – second, inner layer of dense fibrous
tissue with a single layer of flat mesothelial cells on its
inner surface; it is separated from the outer layer to
form the large venous sinuses of the brain; it is also
reflected inward to extend into large fissures of the
brain as partitions (falx cerebri, tentorium cerebelli)
• it is separated from the arachnoid by a thin space,
subdural space
• its internal surface is covered by simple squamous
epithelium of mesenchymal origin
Arachnoid
• is a thin, net-like membrane devoid of blood
vessels
• its outer surface is smooth, but from its inner
surface runs thin, branching threads & ribbon-like
strands attached to the pia
• its surface are covered by simple squamous
epithelium of mesenchymal origin
• microscopically, it has a cobweb-like appearance;
the arachnoid bridges the sulci & fissures in the
surface of the brain & spinal cord forming
subarachnoid spaces of various extent termed
cisternae; the subarachnoid spaces are filled with
CSF
• in some areas, it perforates the dura mater
forming protrusions that terminate in venous
sinuses in the dura mater; the protrusions
containing centrally located trabeculae are called
arachnoidal villi/Pacchonian granulations or
corpuscles
• its function is to transfer CSF to the blood of the
venous sinuses
Pia mater
• is a thin, CT net that is closely adherent to the
surface of the brain & spinal cord
• it contains a large number of blood vessels, from
which most of the blood of the underlying nervous
tissue is supplied
• attached to this are the inner strands of the
arachnoid; because they are intimately related,
they are often considered as a single entity called
pia-arachnoid
• its main elements are interlacing collagenous
bundles surrounded by a fine elastic network;
among the cells are fibroblasts & fixed
macrophages, numerous along the pial blood
vessels
• the blood vessels penetrate the CNS through
tunnels covered by pia mater termed the
perivascular spaces; before the blood vessels are
transformed into capillaries, the pia mater
disappears; in the CNS, the blood capillaries are
completely covered by expansions of the
neuroglial cell process
 The
Meninges
Nerves of the Meninges:
• the dura & pia mater are richly supplied with nerves
• all vessels of the pia & of the choroid plexus are surrounded by
extensive nerve plexuses in the adventitia; also present are sensory,
non-encapsulated nerve terminations
• axons originate in the carotid & vertebral plexuses, & in certain
cranial nerves and belong to the sympathetic system
Blood-Brain Barrier
• it prevents the passage of certain substances from the blood to
nerve tissue
• it results from the reduced permeability that is a property of blood
capillaries of nerve tissue; occluding junctions, which provide
continuity between the endothelial cells, represent the main
structural component of the barrier; the cytoplasm of these
endothelial cells does not have the fenestrations found in many
other locations
• deeper within the brain wall, the pericapillary
spaces are scarcely larger than the other cleft-like
intercellular spaces of nervous tissue; in these
areas, the basal lamina of the capillaries is often
fused with the basal lamina of the neural tissue
border & surrounded by flattened cellular
extensions of astrocytes, the outer glia limitans
a. these cells are avenues of nutrient passage or ion
transport from blood vessels to neuron
b. the mosaic of applied cellular processes constitutes the
barrier for the passage of materials from blood vessels
to brain parenchyma, the BBB
Choroid Plexus
• there are places where the wall of the brain retain
its embryonic character as a thin, non-nervous
epithelium; this part of the brain wall is the lamina
epithelialis; the pia mater covering it is very
vascular & is termed tela choroidea; the vascular
tuft of capillaries from the pia mater covered by
the lamina epithelialis & pushing inward into the
cavity of the ventricles constitute the choroid
plexus
• it is found in the roof of the 3rd & 4th ventricles,
and in part of the wall of the 2 lateral ventricles;
the tela choroidea is much folded & invaginated
into the ventricle, so that the free surface exposed
to the ventricular fluid is large with tortuous
vessels & a rich capillary net
 Low magnification of the choroid plexus
(red arrow)

Cerebellum
(arrow)
• it is composed of loose CT of the pia mater,
covered by a simple cuboidal or low columnar
epithelium of neural tube origin; the epithelial
cells possess numerous irregular microvilli & there
are junctional complexes near their free ends; the
capillaries beneath the epithelium are unlike those
found elsewhere in the brain, they have thin walls
& fenestrations or pores closed by thin
diaphragms; the endothelial cells are held
together by tight junctions; these are the site of
“blood-CSF barrier”
• its CT is quite cellular, containing many
macrophages; they engulf intravenously injected
supravital dyes (trypan blue)
• its main function is to secrete CSF by the epithelial
cells covering the plexuses
 The Choroid
Plexus
A capillary tuft
surrounded by
Ependymal Cells
The Choroid Plexus – Capillaries surrounded by
Ependymal Cells (arrow)
Cerebrospinal Fluid
• it is the fluid elaborated by the choroid plexuses
that completely fills the ventricles, the central
canal of the spinal cord, the subarachnoid space,
& the perivascular space
• it is important for the metabolism of the CNS,
protecting the nervous system from concussions &
mechanical injuries; it bathes & suspends the CNS,
thus cushioning the nervous tissue against trauma
• its amount is variable, estimated at 80 – 150ml; it
is slightly viscous, has a low specific gravity (1.004
– 1.008), contains traces of proteins, small
quantities of inorganic salt & dextrose, and a few
lymphocytes; it resembles the aqueous humor of
the eye more closely than it does any other fluid
of the body
• its sources are primarily the blood vessels of the
choroid plexus, the pia mater and the brain
substance; it is constantly renewed, circulating
slowly through the brain ventricles, and through
the meshes of the subarachnoid space
*ventricular fluid normally flows from the lateral
ventricles of the cerebral hemispheres, through
the foramina of Monroe  3rd ventricle

Fluid is added from the choroid plexus of the 3rd

ventricle, it passes through the Sylvian aqueduct
 4th ventricle  cisterna magna  subarachnoid
space  diffuse into all directions
 *some may enter extracranial lymphatics through
perineural spaces within the cranial nerve roots;
part may reach the nasal cavity along the sheaths
of the olfactory nerve filaments; most passes
directly into the large endocranial venous sinuses
through the arachnoidal villi or Pacchonian
granulations – the villi provides the main pathway
for the rapid flow of the CSF directly into the
venous circulation
• the nerve tissue is completely devoid of lymphatic
vessels; fluid from the capillaries seeps through
the tissue but does not collect in lymphatic
channels, it goes to the perivascular spaces (pia
mater) that open freely at the brain surface into
the subarachnoid space
Brain Ventricles
• central canal/ventricle of the spinal cord in the
adult is small or may appear obliterated; has no
important function
• in normal adult, the ventricular cavities of the
brain form a continuous channel for the flow of
CSF
• the cavity is dilated in the following regions:
a. (2) lateral ventricles – cerebral hemisphere
b. 3rd ventricle – thalamus
c. 4th ventricle – medulla oblongata & pons varolli
*in these 4 regions, the choroid plexuses develop &
from them the ventricular fluid is derived
 Reaction of Neural Tissue to Injury
A. Changes at the site of lesion
• there is a short period during which axoplasm
leaks from the cut ends of the axon following its
uncomplicated interruption
• retraction of the axon & the axolemma appears to
fuse over the severed ends (sealing them)
• damning up of axonal material behind the fused
membranes, so that there is a distinct swelling or
dilatation of the axon within 12 – 24 hours; these
swellings contain a variety of cytoplasmic
organelles termed, retraction bulbs
• in higher vertebrates, no significant regeneration takes
place; within a day or two, the proximal end of the severed
axon degenerates as far back as the first collateral branch
of the axon
• at the site of the injury, the supporting & other non-neural
cells become activated; they participate in the removal of
the neuronal debris, in the formation of a “glial scar” &
possibly in the process of regeneration
• the principal cells of the CNS principally involved are:
a. astrocytes – which may be stimulated to proliferate &
become actively phagocytic; its processes expand to fill the
vacated area to form a dense “glial scar”* which bridges
across the traumatized zone (if the area is too large, they
effectively seal off the damaged area as an encysted space)
b. oligodendrocytes – responsible for sequestering
large masses of cellular debris by forming myelin
ensheathments* around them
c. pericytes
d. blood-borne phagocytes (polymorphonuclear
leukocytes & other macrophages) – invade the
tissue if there has been some damage in the
neighboring capillaries
e. glial cells – initiate a vigorous repair process once
the necrotic tissue has been phagocytosed
*these glial responses are believed to be the causes
that prevent or seriously limit central neural
regeneration
• in the PNS, the Schwann cells show similar prompt
response by actively proliferating & phagocytosing
the breakdown products of the degeneration of
the nerve cells; they form new sheaths for the
regenerating axons
B. Reaction in the Distal Segment
• the entire distal segment will undergo Wallerian
degeneration
• the earliest changes occur at the axon’s terminals
& not close to the injury
• terminal degeneration takes several forms; within
12 – 24 hours after axotomy,
*the earliest changes in the form of a swelling &
possibly some loss of synaptic vesicles; the closer
to the terminals the axon is interrupted, the more
rapidly the degenerative changes appear
 a. there may be marked increase in the number of neurofilaments in the
terminals – this accounts for the increase argyrophilia of degenerating axon
terminals
b. a corresponding decrease in the number of synaptic vesicles
*later, the whole terminal may become filled with filaments & in
silver preparations, appear as a swollen degenerating end bulb
• another reaction involves a progressive increase in the density of
axoplasmic matrix of the terminal & a concomitant loss of the
remaining synaptic vesicles
• in myelinated fibers, the surrounding myelin
sheath degenerate more electron-dense, the
normally smooth contour of the axon becomes
more & more irregular with fusiform swellings &
constrictions, finally breaking up into numerous
short fragments (accounts for the characteristic
fragmented appearance of degenerating nerve
tracts, useful in tracing pathways in the CNS) =
appearance of clefts between the adjoining
lamellae
• the fragmentation of the myelin sheath, & an
alteration in its lipid composition, form the basis
of the so-called Marchi technique, another
method for tracing neural pathways
C. Degenerative changes in the Proximal segment of
the Axon
• the axon proximal to the site of transection may
either degenerate completely or show only
relatively main changes in the region adjoining the
traumatized zone depending on the reaction of
the nerve cell soma
• the axon will degenerate in the proximo-distal
sequence starting near the initial segment should
the parent cell die
• the appearance of the degeneration is essentially
the same as that seen in the distal segment, it is
generally referred to as indirect Wallerian
degeneration
• in case the cell body survives the injury, the axon
appears to degenerate only as far back as its first
collateral branch, proximal to the site of
transection
D. Reaction to Axotomy of the Nerve Cell Soma
• Chromatolysis – is the reaction usually seen in
motor neurons, in sensory ganglion cells & in a
number of large central nerve cells in the brain
stem & spinal cord
• it consists of a progressive breakdown of the Nissl
substance, a tendency for the nucleus to become
more eccentric (moving away from the axon
hillock), and swelling of the perikaryon
• the cell appears globular having lost its usual
angular profile, with the nucleus pressing against
the cell membrane & with only a narrow rim of
Nissl material around the perimeter of the cell or
in a “cap” over the nucleus; this is the appearance
of the neuron in its fully developed state with the
whole process taking about 2 weeks to develop
Cell Death – it follows axon section within a few
days & its removal by glial action; cytological
changes vary but characteristically, the nucleus
becomes pyknotic, the Nissl substance is lost &
the perikaryon shrinks dramatically; these changes
are accompanied by gliosis or marked glial
proliferation which persists following the removal
of the neuronal debris
E. Trans-synaptic/Transneuronal Degenerations
• distinct atrophic or degenerative changes have been observed in
the neurons that are synaptically related to those whose axons
were interrupted (anterograde/retrograde); effects may extend
beyond the first synapse = secondary or tertiary transneuronal
effects