This document discusses the degeneration and regeneration of nerve fibers following injury. It describes the various types of nerve injuries classified based on severity from first to fifth degree. When an axon is injured, degenerative changes occur in the distal segment, proximal segment, and nerve cell body. The distal segment undergoes Wallerian degeneration where the axon breaks down. Regeneration is possible if the nerve cell body and nucleus remain intact and the cut ends are within 3mm and aligned. Peripheral nerves can regenerate guided by Schwann cells, while regeneration is more limited in the central nervous system.
2. SLOâs
ďś INTRODUCTION
ďś CLASSIFICATION OF NERVE INJURIES
ďś INJURY OF THE NERVE CELLBODY
ďś INJURY OF THE NERVE CELLPROCESS
ďś CHANGES IN THE DISTAL SEGMENT OF THEAXON
ďś CHANGES IN THE PROXIMAL SEGMENT OF THEAXON
ďś CHANGES IN THE NERVE CELL BODY
ďś RECOVERY OF THE NEURONS FOLLOWING INJURY
ďś REGENERATION OF AXONS IN THE PERIPHERALNERVES
ďś REGENERATION OF AXONS IN THE CNS
WALLERIAN
DEGENERATION
REGENERATION
3. INTRODUCTION
ďľ Neuron is the basic functional unit of the nervous system.
ďľ In the mature human, if it is destroyed, it is not replaced.
ďľ When a nerve fiber is injured, various changes occur in the nerve
fiber and nerve cell body.
ďľ All these changes are together called the degenerative changes.
ďľ It may be injured due to various reasons(cutting, crushing, pull &
pressure).
ďľ These injuries may damage a nerve variously & the injury is
classified according to the extent of the damage.
4. Causes for Injury
â˘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.
5.
6. Coverings of Nerve
â˘The whole nerve is covered by
tubular sheath, formed by a
areolar membrane.
â˘This sheath is called
epineurium.
â˘Each fasciculus is covered by
perineurium and
â˘each nerve fiber (axon) is
covered by endoneurium
7. DEGREES OF INJURY
â˘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
â˘Second degree is due to the prolonged severe
pressure, Also called axonotmesis.
â˘which causes Wallerian degeneration.
â˘However, the endoneurium is intact.
â˘Repair and restoration of function take about
18 months.
10. THIRD DEGREE
â˘In this case, the endoneurium is interrupted.
â˘Epineurium and perineurium are intact.
â˘After degeneration, the recovery is slow and poor
or incomplete.
â˘Third, fourth and fifth degrees of injury are
called neurotmesis.
11. FOURTH DEGREE
â˘This type of injury is more severe.
â˘Epineurium an perineurium are also
interrupted.
â˘Fasciculi of nerve fibers are disturbed and
disorganized.
â˘Regeneration is poor or incomplete.
12. FIFTH DEGREE
â˘Fifth degree of injury involves complete
transaction of the nerve trunk with loss of
continuity.
â˘Recovery is not possible without an
appropriate surgical treatment
13.
14.
15. INJURY OF THE NERVE CELLBODY
ďľSevere damage of the nerve cell body may result in
degeneration of the entire neuron.
ďľIn the CNS, the tissue macrophages (microglial cells)
remove the debris, & the neighboring astrocytes replace
the neuron with scar tissue
ďľIn the PNS, the tissue macrophages remove the debris, &
the local fibroblasts replace the neuron with scar tissue
16. INJURY OF THE NERVE CELLPROCESS
ď§ If the axon of the nerve cell is divided,
degenerative changes will take place in
ď§ Distal segment of the axon
ď§ A portion of the axon proximal to the injury
ď§ 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. ďľSchwann cells now begin to proliferate rapidly &
axonal sprouts grow from the proximal stump,
enter the distal stump, & grow toward the nerve's
end-organs
ďľIf 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
ďľThe 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
â˘The term regeneration refers to regrowth of lost
or destroyed part of a tissue.
â˘The injured and degenerated nerve fiber can
regenerate.
â˘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
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
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.