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NERVOUS TISSUE

– Nervous tissue makes up the nervous system.


– Nervous tissue consists of:
1. Two types of cells population:
i. Neurons (Nerve cells) and
ii. Supportive cells (Neuroglial cells)
2. Nerve fibers.
3. Nerve endings:
i. Sensory nerve endings or Receptors and
ii. Motor nerve endings on effector organs.
NERVOUS TISSUE
– Nervous tissue of the CNS does not contain CT other than
that in the meninges and in the walls of large blood vessels.

– Fibroblasts/cytes or collagenous and elastic fibers are


absent, which is quite unlike other tissues.

– Because of the absence of connective tissues and CT fibers,


fresh CNS tissue has a very soft, somewhat jelly-like
consistency.
This is nervous tissue of the anterior horn of the gray matter of spinal
cord showing large neurons and numerous small glial cells
EXTERNAL PYRAMIDAL CELL LAYER OF CEREBRAL CORTEX
NEURONS
– The nerve cell or neuron is the structural and functional unit of the
nervous system for receiving, processing and conducting of stimuli.

– They are responsible for releasing neurotransmitters.

– Are both the smallest and the largest , the longest and the long
living cells.

 The neuron has two highly developed physiologic properties:

– Irritability: is the capacity to generate nerve impulses in


response to various stimuli.

– Conductivity: is the ability to transmit the impulses along the


processes of the neuron.
STRUCTURE OF NEURON
• Typical neuron is formed of:

1. Cell body called perikaryon or soma which contains the nucleus


& other organelles.

2. One or more dendrites: which receive stimuli and carry


impulses towards the cell body.

3. Single Axon: arising from the cell body, specifically called axon
hillock and conducts the impulses away from it.

– A dense network of fibers from processes of both neurons and


glial cells fills the inter-neuronal space of the CNS and is called
the neuropil.
NEURON
NODE OF RANVIER
FINE STRUCTURE OF A NEURON
The Cell Body of a neuron contains:
1. Euchromatic vesicular nucleus (open-face nucleus, Owl-eye
nucleus) with conspicuous nucleolus.
2. Very well developed perinuclear Golgi Complex.
3. Mitochondria: are found throughout the neuron i.e. in cell body
and its processes.
4. Rough Endoplasmic Reticulum (RER) is present only in cell body
and dendrites and not present in the axon and axon hillock. RER
& ribosomes appear as large clumps of basophilic material called
Nissl substance
5. Neurofibrils and neurofilaments: are distributed throughout the
neuron and appear by light microscope.
6. Microtubules: are found throughout the neuron.
– extend the entire length of the axon and provide the rail
track along the substrate move in axoplasmic transport .
Owl (ጉጉት/jajjuu)
Spinal Ganglion (Dorsal Root Ganglion)
Nissl substance/bodies/granules:
– Are granular basophilic substance consisting of cisternae
of RER arranged in parallel array and attached
polyribosomes.

– found throughout the cytoplasm of the perikaryon and


dendrites of most neurons but is absent from the axon and
axon hillock.

– represent the sites of protein synthesis in neurons.

– The protein is then transported down the length of the


axon for use in metabolism or repair in this region or in
some instances is secreted.
1.THE AXON (AXIS CYLINDER):
– is the efferent process of the neuron which carries the impulse
away from the cell body.
– It originates from the cell body by a conical portion called “axon
hillock”.
– is a single, thin, usually long process with a uniform size.
– gives some collateral branches (at right angle) and many terminal
branches (axon terminals).
– It is surrounded with a membrane called axolemma and its
cytoplasm is called axoplasm.
– It contains mitochondria, microtubules and neurofibrils and
neurofilaments.
– It does not contain Nissl granules (RER), it depends on the proteins
synthesized in the cell body which is conveyed by the aid of the
movements of microtubules throughout the axon by a process
called axoplasmic transport.
AXOPLASMIC TRANSPORT
– There is a lively bidirectional transport of small and large
molecules along the axon.
• anterograde transport
– Organelles and macromolecules synthesized in the cell
body move by along the axon from the perikaryon to the
axon/synaptic terminals.
• Retrograde transport
– carries certain other macromolecules, such as material
taken up by endocytosis (including viruses and toxins),
from the periphery to the cell body.
AXOPLASMIC TRANSPORT
– Axonal transport in both directions utilizes motor proteins
attached to microtubules.

– Kinesin, a microtubule-activated ATPase, attaches to


vesicles and allows them to move along microtubules
in an axon away from the perikaryon.

– Dynein is a similar ATPase that allows retrograde


transport in axon, toward the cell body.

– Anterograde and retrograde transport both occur fairly

rapidly, at rates of 50 to 400 mm/day.


TYPES OF NERVE FIBERS
– are processes of neurons mainly axons.
– Based on their thickness, rate of impulse transmission and
other characteristics there are three types of fibers.
1. Type A fibers
– are thick, myelinated fibers with long internodes
– conduct impulses at a high velocity (15-100 m/sec)
– include somatic afferent and efferent fibers.
2. Type B fibers
– have a smaller diameter and a thinner myelin sheath
than type A fibers.
– conduct impulses at a moderate velocity (3-14 m/sec)
– include preganglionic autonomic efferents
3. Type C fibers
– are thin non-myelinated postganglionic autonomic fibers
– conduct impulses at slow velocity (0.5-2 m/sec)
2. DENDRITES:
– are afferent processes of the neuron which carry the
impulse to the neuron cell body.
– are multiple, short, thick processes and their thickness
decreases towards its end.
– have many branches with spines.
– contain Nissl granules, mitochondria, microtubules and
neurofibrils and neurofilaments.
CLASSIFICATION OF NEURONS
I. According to the neuronal polarity (number of
processes):
1. Pseudo-unipolar neurons: which have single process, then divides
into axon and dendrite. They are present in dorsal root ganglion (also
called spinal ganglion or sensory ganglion).

2. Bipolar neurons: they are spindle-shaped with two processes; one


axon and one dendrite.

– They are present in areas of special sensations as: retina,


olfactory mucosa and inner ear.

3. Multipolar neurons: they have several processes.


– They are the most common types of neurons
– present in the grey matter of CNS and autonomic ganglia
Spinal Ganglion cells are examples of pseudounipolar neurons
II. Based on the shape of the cell body, neurons can be
classified as:
a. Pyramidal cells: as in cerebral cortex.
b. Purkinje (flask-shaped) cells; as in cerebellar cortex.
c. Stellate cells: as in Gray matter of spinal cord and
cortex of brain and autonomic ganglia.
– Each Purkinje cell has a rounded
– cell body,
– a slender axon that projects through the granular layer into the
white matter, and
– three to five main dendrites that divide into an elaborate
dendritic arborizations.
PYRAMIDAL CELLS IN THE CEREBRAL CORTEX
III. According to the length of their axons:
1. Golgi type 1 neurons: have very long axons

2. Golgi type 2 neurons: have very short axons

Golgi type І neurons


– have long axons that begin in the CNS and terminate at a
great distance far away in the CNS or peripherally.
– anterior horn motor neurons and cerebral pyramidal cells are
examples of Golgi type I neurons.
Golgi type II neurons
– have short axons that begin and end in restricted regions
within the CNS. E.g in cerebral and cerebellar cortices and
retina.
IV. According to their function (based the direction in
which they carry impulse), neurons can be classified
into:

A. Sensory (afferent) neurons: which receive stimuli from the


external environment and from inside the body and convey
the impulse to CNS.

B. Motor (efferent) neurons: which convey impulses to


effector organs (muscles and glands).

C. Interneurons/association/integrating neurons: carry


impulse from one neuron to the other, include neurons in
retina and neurons between the above two in CNS.
NEUROGLIAL CELLS (NEUROGLIA) OR SUPPORTING CELLS OF
NERVOUS TISSUE
– Glial cells are 10 times more abundant than neurons.

– There are six kinds of glial cells: Glial cells in the CNS: astrocytes,
oligodendrocytes, microglia and ependymal cells; Glial cell in the
PNS: Schwann cells and satellite cells.

– Supportive and protective cells

– Can go through mitosis

– Surround other nerve cells

– Line brain and spinal cord nerves

– Produce myelin, -Phagocytic -Source of brain cancers


CENTRAL NEUROGLIA (NEUROGLIAL CELLS IN CNS)
1. ASTROCYTES
• most abundant glial cell in CNS
• cover entire brain surface and most non-synaptic regions of
the neurons in the gray matter of the CNS
• diverse functions
– form a supportive framework of nervous tissue
– have extensions (perivascular feet) that contact blood
capillaries that stimulate them to form a tight seal called
the blood-brain barrier
– convert blood glucose to lactate and supply this to the
neurons for nourishment
– nerve growth factors secreted by astrocytes promote
neuron growth and synapse formation
– communicate electrically with neurons and may
influence synaptic signaling
– regulate chemical composition of tissue fluid by
absorbing excess neurotransmitters and ions
– astrocytosis or sclerosis – when neuron is
damaged, astrocytes form hardened scar tissue and
fill space formerly occupied by the neuron
– Morphology of the processes allows astrocytes to be classified
as
• fibrous (relatively few and straight processes) or
• protoplasmic (numerous branching processes),
– but functional differences between the two are not clear.
Fibrous Astrocytes:
– are astrocytes with relatively few long
processes
• have few and long straight processes
which branch infrequently.
– mainly found in white matter.
– have euchromatic nuclei and a
vascular pedicle, i.e. one process ends
on a small blood vessel (perivascular
feet).
– tumors arising from these astrocytes,
fibrous astrocytomas, account for about
80% of adult primary brain tumors.
Fibrous astrocytes in the white matter of the brain
Protoplasmic Astrocytes:
– named because of their abundant
cytoplasm with many short
branching processes.

– more prevalent in the outermost


covering of brain called gray matter.

– Their abundant cytoplasm is rich in


cytoplasmic granules called
gliosomes which are considered as
lysosomes.
Protoplasmic astrocyte in
the gray matter of the
brain. a. This schematic
drawing shows the foot
processes of the
protoplasmic astrocyte
terminating on a blood
vessel and the axonal
process of a nerve cell.
The foot processes
terminating on the blood
vessel contribute to the
blood–brain barrier. The
bare regions of the vessel
as shown in the drawing
would be covered by
processes of neighboring
astrocytes, thus forming
the overall barrier
Astrocytes stained with antibodies against GFAP (grey mater)
2. OLIGODENDROCYTES or
OLIGODENDRIA
• form myelin sheaths in CNS
• each arm-like process wraps
around a nerve fiber forming
an insulating layer that
speeds up signal conduction
• A single oligodendrocyte can
contribute myelination of up to 50
axons which may belong to the
same or different fiber tracts.
– predominant in CNS white
matter as well in the grey matter.
A single oligodendrocyte contributes to the myelination of
several axons
– Finally, the nodes of Ranvier in the CNS are larger
than those in the PNS.
– The larger areas of exposed axolemma thus make saltatory
conduction even more efficient in the CNS.
– unmyelinated neurons in the CNS are often found to be bare
 that is, they are not embedded in glial cell processes.

– In the CNS there is lack of:-


– supporting cells around unmyelinated axons
– external lamina material and
– connective tissue

– helps to distinguish the CNS from the PNS in histologic


sections and in TEM specimens.
3. MICROGLIA (MICROGLIAL CELLS)
– Are irregular cells with fine highly branched fragile
processes and
– thin, cigar-shaped (elongated) dark nucleus.
– somewhat less numerous than oligodendrocytes or
astrocytes but more evenly distributed throughout gray
and white matter.
• small, wandering macrophages formed white blood cell
called monocytes
• thought to perform a complete checkup on the brain tissue
several times a day
• wander in search of cellular debris to phagocytize
– Microglia considered
part of the mononuclear
phagocytotic system and
originate from
granulocyte/monocyte
progenitor (GMP) cells.
– Microglia precursor cells
enter the CNS
parenchyma from the
vascular system
– belong to the same family as
macrophages and other
antigen-presenting cells.
NEUROGLIA

1. Microglia 3. Neuron cell


body

4. Microglia : cell
body

5. Microglial
processes showing
the characteristic
2. Endothelial cell “spiny” appearance
of a capillary
6. Capillary

7. Erythrocytes in
a capillary

Microglia of the brain


47
4. EPENDYMAL CELLS (EPENDYMOCYTES)
– form the epithelial-like lining of the fluid filled cavities of
the CNS
– the ventricles of the brain and
– central canal of spinal cord).
– a single layer of cuboidal to-low columnar cells
– In some CNS locations, the apical ends:,
• have cilia, which facilitate the movement of cerebrospinal fluid
(CSF), or
• long microvilli, which are likely involved in absorption.
– Ependymal cells are joined apically by tight junctional
complexes similar to those of epithelia to prevent the
entry of proteins to the CSF.
Ependymal Cells lining Central Canal of Spinal Cord
CHOROID PLEXUS
– constitutes pseudoepithelial glandular tissue specialized for
secretion of cerebrospinal fluid (CSF).
– found in the roof and lateral walls of brain ventricles where
the pia mater and ependymal cells come close together with
out intervening nervous tissue.
– This fused meningeal and ependymal tissue is called tela
choroidae.
– consists of loose areolar CT core rich in fenestrated blood
capillaries covered by a simple cuboidal epithelium formed by
the modified ependymal cells known as Tanicytes.
– The tanicytes rest on a basal lamina and apically connected
together by tight (occluding) junctional seals.
CHOROID PLEXUS
PERIPHERAL NEUROGLIA (NEUROGLIAL CELLS IN PNS)
– are the supporting cells within the PNS.
– Include:
– Schwann cells
– Satellite cells
– Enteric neuroglia associated with the ganglia located in
the wall of the alimentary canal;
– Terminal neuroglia/teloglia), which are associated with
the motor end plate and encapsulated sensory nerve
endings, and
– Müller cells (of retina)
5. SATELLITE CELLS OF GANGLIA
– small cuboidal/round cells which form a covering layer
over the large neuronal cell bodies in PNS ganglia.

– derived from the embryonic neural crest cells.

– Although the molecular basis of their support is poorly


understood, they have the following functions:
– trophic or supportive role
– separate ganglionic cells from blood capillaries
– help metabolic exchange between ganglion cells and
blood.
– insulate
Satellite cells in Dorsal Root Ganglion
Satellite Cells: form a layer around ganglion cells and separate
them from blood capillaries. It helps metabolic exchange between
ganglion cells and blood.
6. SCHWANN CELLS (NEUROLEMMA CELLS)

• envelope nerve fibers in PNS


• wind repeatedly around a nerve fiber
• produces a myelin sheath similar to the ones produced
by oligodendrocytes in CNS
• assist in the regeneration of damaged fibers

– have peripheral oval nucleus and basophilic cytoplasm

– Rest on external lamina (similar to basal lamina of epithelial


cells).

– Together with their external lamina surround the axons of


peripheral nerves and look like tubes which envelop the axon.
Four consecutive phases of myelin formation in peripheral
nerve fibers.

59
Glial Cells and Brain Tumors
• tumors - masses of rapidly dividing cells
– mature neurons have little or no capacity for mitosis and
seldom form tumors
• brain tumors arise from:
– meninges (protective membranes of CNS)
– by metastasis from non-neuronal tumors in other organs
– most come from glial cells that are mitotically active
throughout life
• gliomas grow rapidly and are highly malignant
– blood-brain barrier decreases effectiveness of chemotherapy
– treatment consists of radiation or surgery

12-60
DEMYELINATING DISEASES

Reading assignment
NERVE INJURY, DEGENERATION AND REGENERATION (NEURAL
PLASTICITY)

– When a nerve fiber is cut, severed


(crushed) or compressed, several
degenerative changes occur both:
– proximal to the site of injury i.e.
in cell body and proximal part of
the injured axon (retrograde
degeneration).
– distal to the site of injury i.e. in
the nerve fiber (anterograde or
Wallarian degeneration).
Nerve Injuries, degeneration & regeneration

Neural plasticity and reformation of processes are controlled by


several growth factors produced by both neurons and glial cells in a
family of growth factors called neurotrophins.
Reaction to Injury
– Neuronal injury induces a complex sequence of events
termed axonal degeneration and neural regeneration.
– Neurons, Schwann cells, oligodendrocytes, macrophages,
and microglia are involved in these responses.
1. Local degenerative changes: at the site of injury: removal
of debris and proliferation of neurolemma cells.
2. Anterograde degenerative changes: “Wallerian
degeneration”; axons and myelin disintegrate,
macrophages infiltrate the region; Schwann cells de-
differentiate and proliferate and remove fragments.
3. Retrograde degenerative changes: proximal to site of
injury:
ANTEROGRADE cont’d…
– The portion of a nerve fiber distal to a site of injury
degenerates because of interrupted axonal transport.
– Degeneration of an axon distal to a site of injury is called
anterograde (Wallerian) degeneration.
– The first sign of injury, which occurs 8–24 hours after
the axon is damaged, is axonal swelling followed by its
disintegration.
– This leads to breakdown of the axonal cytoskeleton:
Microtubules, neurofilaments, and other cytoskeleton
components are disassembled, resulting in the
fragmentation of the axon.
ANTEROGRADE cont’d…
– When an axon is injured, the blood–nerve barrier is
disrupted along the entire length of the injured axon,
which allows for the influx of these cells into the site of
injury.
– The presence of large numbers of monocyte-derived
macrophages speeds up the process of myelin removal,
which in peripheral nerves is usually completed within 2
weeks.
– In the CNS, inefficient clearance of myelin debris due to
limited access of monocyte-derived macrophages, the
inefficient phagocytic activity of microglia, and the
formation of an astrocyte-derived scar severely restrict
nerve regeneration.
RETROGRADE DEGENERATION
– Are Changes occurring in the cell body and proximal
axon:
– Nissl granules disappear within few days
(chromatolysis).
– Neurofibrils and Golgi apparatus disappear, nucleus
becomes eccentric and begins to degenerate.
– Cell loses its processes and becomes globular.
– Some cells disintegrate completely, but others can
recover after successful re-establishment of
innervation.
– This depends on the site of injury; when the injury
is very close to the cell body, the whole neuron
dies.
Retrograde changes: proximal to site of injury
site:
 Are reactions to nerve injury that may
occur in
1. the proximal axon and is called traumatic
degeneration
2. the cell body which includes:
– Swelling of cell body
– Displacement of the nucleus to periphery –
becomes eccentric.
– Dissolution and redistribution of Nissl bodies
(central chromatolysis)
RETEROGRADE cont’d…
– Retrograde signaling to the cell body of an injured
nerve causes a change in gene expression that initiates
reorganization of the perinuclear cytoplasm.
– Axonal injury also initiates retrograde signaling to the
nerve cell body leading to the upregulation of a gene
called c-jun.
– C-jun transcription factor is involved in early as well as
later stages of nerve regeneration.
– Reorganization of the perinuclear cytoplasm and
organelles starts within a few days.
RETEROGRADE cont’d…
– Initially, Nissl bodies disappear from the center of
the neuron and move to the periphery of the
neuron in a process called chromatolysis.
– Chromatolysis is first observed within 1 to 2
days after injury and reaches a peak at about 2
weeks.
– The changes in the cell body are proportional to
the amount of axoplasm destroyed by the injury;
extensive loss of axoplasm can lead to death of
the cell.
NERVE REGENERATION IN PNS
– Neurilemma (Schwann) cells are essential for
regeneration in peripheral nervous system.
– Because nerve fibres in CNS do not have Schwann Cells,
there is NO efficient regeneration in the brain and spinal
cord.
– Axons from proximal end send many new buds (axonal
sprouts) which pass on the bridges of neurilemma cells,
guided by the tunnels formed by neurilemma cells.
– The new axons enter the tunnels and new myelin is
formed around them.
– The rate of growth of the new axons is l-5 mm per day.
– If new (motor) axons succeed to enter tunnels of
neurilemma which lead to "muscles" and new (sensory)
axons enter the tunnels leading to "sensory endings"
recovery is complete & excellent. If not, recovery of
function will be incomplete.
Re-growth of axons
– After crossing the site of injury, sprouts enter the
surviving cellular bands in the distal stump.
– These bands then guide the neurites to their destination
as well as provide a suitable microenvironment for
continued growth.
– Axonal regeneration leads to Schwann cell
redifferentiation, which occurs in a proximal-to distal
direction.
– Redifferentiated Schwann cells up-regulate genes for
myelin-specific proteins and down regulate c-jun.
– If physical contact is reestablished between a motor neuron and
its muscle, function is usually reestablished.
– Microsurgical techniques that rapidly reestablish intimate
apposition of severed nerve and vessel ends have made
reattachment of severed limbs and digits, with subsequent
reestablishment of function, a relatively common procedure.
– If the axonal sprouts do not reestablish contact with
the appropriate Schwann cells, then the sprouts grow in a
disorganized manner, resulting in the mass of tangled axonal
processes known as traumatic neuroma or amputation neuroma.
– Clinically, traumatic neuroma usually appears as a freely movable
nodule at the site of nerve injury and is characterized by pain,
particularly on palpation.
– Traumatic neuroma of the injured motor nerve prevents
reinnervation of the affected muscle.
THE END!

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