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Degeneration & Regeneration
of
Nerve Fibers
Dr. Pandian M
Dept. of Physiology
DYPMCKOP
SLO’s
 INTRODUCTION
 CLASSIFICATION OF NERVE INJURIES
 INJURY OF THE NERVE CELLBODY
 INJURY OF THE NERVE CELLPROCESS
 CHANGES IN THE DISTAL SEGMENT OF THEAXON
 CHANGES IN THE PROXIMAL SEGMENT OF THEAXON
 CHANGES IN THE NERVE CELL BODY
 RECOVERY OF THE NEURONS FOLLOWING INJURY
 REGENERATION OF AXONS IN THE PERIPHERALNERVES
 REGENERATION OF AXONS IN THE CNS
WALLERIAN
DEGENERATION
REGENERATION
INTRODUCTION
 Neuron is the basic functional unit of the nervous system.
 In the mature human, if it is destroyed, it is not replaced.
 When a nerve fiber is injured, various changes occur in the nerve
fiber and nerve cell body.
 All these changes are together called the degenerative changes.
 It may be injured due to various reasons(cutting, crushing, pull &
pressure).
 These injuries may damage a nerve variously & the injury is
classified according to the extent of the damage.
Causes for Injury
•Injury to nerve fiber occurs due to following
causes:
1. Obstruction of blood flow
2. Local injection of toxic substances
3. Crushing of nerve fiber
4. Transection of nerve fiber.
Coverings of Nerve
•The whole nerve is covered by
tubular sheath, formed by a
areolar membrane.
•This sheath is called
epineurium.
•Each fasciculus is covered by
perineurium and
•each nerve fiber (axon) is
covered by endoneurium
DEGREES OF INJURY
•Depending upon the order of severity nerve
injury classification into five categories its
called Sunderland Classification.
FIRST DEGREE
• It is most common type of injury to the nerves.
• First degree of injury is also called Seddon neuropraxia.
• It is caused by applying pressure over a nerve for a short
period.
• Leading to occlusion of blood flow and hypoxia.
• In this - Axon is not destroyed but mild demyelination occurs.
• It is not a true degeneration.
• Axon looses the function temporarily for a short time, which
is called conduction block.
• The function returns within few hours to few weeks.
SECOND DEGREE
•Second degree is due to the prolonged severe
pressure, Also called axonotmesis.
•which causes Wallerian degeneration.
•However, the endoneurium is intact.
•Repair and restoration of function take about
18 months.
THIRD DEGREE
•In this case, the endoneurium is interrupted.
•Epineurium and perineurium are intact.
•After degeneration, the recovery is slow and poor
or incomplete.
•Third, fourth and fifth degrees of injury are
called neurotmesis.
FOURTH DEGREE
•This type of injury is more severe.
•Epineurium an perineurium are also
interrupted.
•Fasciculi of nerve fibers are disturbed and
disorganized.
•Regeneration is poor or incomplete.
FIFTH DEGREE
•Fifth degree of injury involves complete
transaction of the nerve trunk with loss of
continuity.
•Recovery is not possible without an
appropriate surgical treatment
INJURY OF THE NERVE CELLBODY
Severe damage of the nerve cell body may result in
degeneration of the entire neuron.
In the CNS, the tissue macrophages (microglial cells)
remove the debris, & the neighboring astrocytes replace
the neuron with scar tissue
In the PNS, the tissue macrophages remove the debris, &
the local fibroblasts replace the neuron with scar tissue
INJURY OF THE NERVE CELLPROCESS
 If the axon of the nerve cell is divided,
degenerative changes will take place in
 Distal segment of the axon
 A portion of the axon proximal to the injury
 The cell body from which the axon arises
CHANGES IN THE NERVE CELLBODY
• The changes that occur in the cell body following
injury to its axon are referred to as retrograde
degeneration
• The nissil material becomes fine, granular, &
dispersed throughout the cytoplasm (chromatolysis)
• The nucleus moves toward the periphery of the cell, &
the cell body swells & becomes rounded
• Synaptic terminals are replaced by schwann cells in
the PNS & microglial cells or astrocytes in the CNS
CHANGES IN THE DISTAL SEGMENT OF
THE AXON
• Wallerian degeneration is the changes that occur distally to the site
of damage on an axon
• Axon becomes swollen & irregular; the axon is broken into
fragments, & the debris is digested by surrounding schwann cells
& tissue macrophages
• Entire axon is destroyed within a week
• Myelin sheath is converted into lipid droplets
• The droplets are extruded from the schwann cell & subsequently
are phagocytosed by tissue macrophages
Schwann cells now begin to proliferate rapidly &
axonal sprouts grow from the proximal stump,
enter the distal stump, & grow toward the nerve's
end-organs
If regeneration does not occur, the axon & the
Schwann cells are replaced by fibrous tissue
produced by local fibroblasts
CHANGES IN THE PROXIMAL SEGMENT OF
THE AXON
The changes in the proximal segment of the
axon are similar to those that take place in the
distal segment but extend only proximally
above the lesion as far as the first node of
ranvier
REGENERATION OF NERVE FIBER
•The term regeneration refers to regrowth of lost
or destroyed part of a tissue.
•The injured and degenerated nerve fiber can
regenerate.
•It starts as early as 4th day after injury, but
becomes more effective only after 30 days and is
completed in about 80 days.
CRITERIA FOR REGENERATION
Regeneration is possible only if certain criteria are fulfilled by
the degenerated nerve fiber:
1. Gap between the cut ends of the nerve should not exceed 3 mm
2. Neurilemma should be present; as neurilemma is absent in
CNS, the regeneration of nerve does not occur in CNS
3. Nucleus must be intact; if it is extruded from nerve cell body,
the nerve is atrophied and there generation does not occur
4. Two cut ends should remain in the same line.
Regeneration does not occur if any one end is moved away.
RECOVERY OF NEURONS FOLLOWING
INJURY
• The recovery of the nerve cell body &
regeneration of its processes may take several
months.
• RNA & protein synthesis is accelerated
• A reconstitution of the original nissil structure
• A decrease in the swelling of the cell body
• A return of nucleus to its characteristic central
position
REGENERATION OF AXONS IN
PERIPHERAL NERVES
• Depend on endoneurial tubes & possessed by schwann cells
• The following meachanisms are involved:
1. The axons are attracted by chemotropic factors secreted by the
schwann cells in the distal stump.
2. Growth-stimulating factors exist within the distal stump, &
3. Inhibitory factors are present in the perineurium to inhibit the
axons from leaving the nerve
REGENERATION OF AXONS IN
THE CNS
• Central axons may not be as good at regeneration as peripheral
axons
• The regeneration process is aborted by:
1. Failure of oligodendrocytes to serve in the same manner as
schwann cells
2. Laying down of scar tissue by the active astrocytes
3. Absence of nerve growth factors in the CNS
4. Neuroglial cells may produce nerve growth-inhibiting factors
THANK YOU . . .

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Degeneration & regeneration of nerve fiber.ppt by Dr. PANDIAN M.

  • 1. Degeneration & Regeneration of Nerve Fibers Dr. Pandian M Dept. of Physiology DYPMCKOP
  • 2. SLO’s  INTRODUCTION  CLASSIFICATION OF NERVE INJURIES  INJURY OF THE NERVE CELLBODY  INJURY OF THE NERVE CELLPROCESS  CHANGES IN THE DISTAL SEGMENT OF THEAXON  CHANGES IN THE PROXIMAL SEGMENT OF THEAXON  CHANGES IN THE NERVE CELL BODY  RECOVERY OF THE NEURONS FOLLOWING INJURY  REGENERATION OF AXONS IN THE PERIPHERALNERVES  REGENERATION OF AXONS IN THE CNS WALLERIAN DEGENERATION REGENERATION
  • 3. INTRODUCTION  Neuron is the basic functional unit of the nervous system.  In the mature human, if it is destroyed, it is not replaced.  When a nerve fiber is injured, various changes occur in the nerve fiber and nerve cell body.  All these changes are together called the degenerative changes.  It may be injured due to various reasons(cutting, crushing, pull & pressure).  These injuries may damage a nerve variously & the injury is classified according to the extent of the damage.
  • 4. Causes for Injury •Injury to nerve fiber occurs due to following causes: 1. Obstruction of blood flow 2. Local injection of toxic substances 3. Crushing of nerve fiber 4. Transection of nerve fiber.
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  • 6. Coverings of Nerve •The whole nerve is covered by tubular sheath, formed by a areolar membrane. •This sheath is called epineurium. •Each fasciculus is covered by perineurium and •each nerve fiber (axon) is covered by endoneurium
  • 7. DEGREES OF INJURY •Depending upon the order of severity nerve injury classification into five categories its called Sunderland Classification.
  • 8. FIRST DEGREE • It is most common type of injury to the nerves. • First degree of injury is also called Seddon neuropraxia. • It is caused by applying pressure over a nerve for a short period. • Leading to occlusion of blood flow and hypoxia. • In this - Axon is not destroyed but mild demyelination occurs. • It is not a true degeneration. • Axon looses the function temporarily for a short time, which is called conduction block. • The function returns within few hours to few weeks.
  • 9. SECOND DEGREE •Second degree is due to the prolonged severe pressure, Also called axonotmesis. •which causes Wallerian degeneration. •However, the endoneurium is intact. •Repair and restoration of function take about 18 months.
  • 10. THIRD DEGREE •In this case, the endoneurium is interrupted. •Epineurium and perineurium are intact. •After degeneration, the recovery is slow and poor or incomplete. •Third, fourth and fifth degrees of injury are called neurotmesis.
  • 11. FOURTH DEGREE •This type of injury is more severe. •Epineurium an perineurium are also interrupted. •Fasciculi of nerve fibers are disturbed and disorganized. •Regeneration is poor or incomplete.
  • 12. FIFTH DEGREE •Fifth degree of injury involves complete transaction of the nerve trunk with loss of continuity. •Recovery is not possible without an appropriate surgical treatment
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  • 15. INJURY OF THE NERVE CELLBODY Severe damage of the nerve cell body may result in degeneration of the entire neuron. In the CNS, the tissue macrophages (microglial cells) remove the debris, & the neighboring astrocytes replace the neuron with scar tissue In the PNS, the tissue macrophages remove the debris, & the local fibroblasts replace the neuron with scar tissue
  • 16. INJURY OF THE NERVE CELLPROCESS  If the axon of the nerve cell is divided, degenerative changes will take place in  Distal segment of the axon  A portion of the axon proximal to the injury  The cell body from which the axon arises
  • 17. CHANGES IN THE NERVE CELLBODY • The changes that occur in the cell body following injury to its axon are referred to as retrograde degeneration • The nissil material becomes fine, granular, & dispersed throughout the cytoplasm (chromatolysis) • The nucleus moves toward the periphery of the cell, & the cell body swells & becomes rounded • Synaptic terminals are replaced by schwann cells in the PNS & microglial cells or astrocytes in the CNS
  • 18. CHANGES IN THE DISTAL SEGMENT OF THE AXON • Wallerian degeneration is the changes that occur distally to the site of damage on an axon • Axon becomes swollen & irregular; the axon is broken into fragments, & the debris is digested by surrounding schwann cells & tissue macrophages • Entire axon is destroyed within a week • Myelin sheath is converted into lipid droplets • The droplets are extruded from the schwann cell & subsequently are phagocytosed by tissue macrophages
  • 19. Schwann cells now begin to proliferate rapidly & axonal sprouts grow from the proximal stump, enter the distal stump, & grow toward the nerve's end-organs If regeneration does not occur, the axon & the Schwann cells are replaced by fibrous tissue produced by local fibroblasts
  • 20.
  • 21. CHANGES IN THE PROXIMAL SEGMENT OF THE AXON The changes in the proximal segment of the axon are similar to those that take place in the distal segment but extend only proximally above the lesion as far as the first node of ranvier
  • 22. REGENERATION OF NERVE FIBER •The term regeneration refers to regrowth of lost or destroyed part of a tissue. •The injured and degenerated nerve fiber can regenerate. •It starts as early as 4th day after injury, but becomes more effective only after 30 days and is completed in about 80 days.
  • 23. CRITERIA FOR REGENERATION Regeneration is possible only if certain criteria are fulfilled by the degenerated nerve fiber: 1. Gap between the cut ends of the nerve should not exceed 3 mm 2. Neurilemma should be present; as neurilemma is absent in CNS, the regeneration of nerve does not occur in CNS 3. Nucleus must be intact; if it is extruded from nerve cell body, the nerve is atrophied and there generation does not occur 4. Two cut ends should remain in the same line. Regeneration does not occur if any one end is moved away.
  • 24. RECOVERY OF NEURONS FOLLOWING INJURY • The recovery of the nerve cell body & regeneration of its processes may take several months. • RNA & protein synthesis is accelerated • A reconstitution of the original nissil structure • A decrease in the swelling of the cell body • A return of nucleus to its characteristic central position
  • 25. REGENERATION OF AXONS IN PERIPHERAL NERVES • Depend on endoneurial tubes & possessed by schwann cells • The following meachanisms are involved: 1. The axons are attracted by chemotropic factors secreted by the schwann cells in the distal stump. 2. Growth-stimulating factors exist within the distal stump, & 3. Inhibitory factors are present in the perineurium to inhibit the axons from leaving the nerve
  • 26. REGENERATION OF AXONS IN THE CNS • Central axons may not be as good at regeneration as peripheral axons • The regeneration process is aborted by: 1. Failure of oligodendrocytes to serve in the same manner as schwann cells 2. Laying down of scar tissue by the active astrocytes 3. Absence of nerve growth factors in the CNS 4. Neuroglial cells may produce nerve growth-inhibiting factors
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  • 30. THANK YOU . . .

Editor's Notes

  1. Distal nerve segment post-nerve injury. A motor neuron (left) innervates muscle tissue (right) via an axon myelinated by Schwann cells (center). After sustaining an injury, the distal nerve segment will degenerate into amorphous debris. Hematogenous macrophages (green) are recruited from circulation and enter the distal stump. Macrophages make the microenvironment more permissive for axonal regeneration by clearing cellular debris and releasing cytokines and neurotrophic factors. Axons regenerate with the guidance of Schwann cells and the aid of macrophages that release neurotrophic factors and eliminate debris that poses a physical barrier and releases inhibitory signaling to the regenerating axon
  2. 1. The Chondroitin Sulphate proteoglycans (CSPGs) which is blocking the regeneration process of the nerve and this CSPGs could change the structure by the enzyme called Chondroitinase. 2ns strategy is to introduce factors to boost the capacity of the damaged neuron themselves i.e smuggle the intergrins back to damaged neuron to recover. Although researcher adding the Growth factors themselves i.e. Ptn IGF 1 and osteopontin those shown axon regrowth. The 3rd one is by studied in rats that mesenchymal stem cells (MSCs) always avail at the junction of the damaged area to protect against secondary damage causes by Immune system. This MSCs also promote axon regeneration and repair the axon insulating layers of myelin, and they directly transform to form new neuron. This study is in due to reported in human study soon.