Degeneration and regeneration of peripheral nerves.pdf

About wallerian degeneration

1. REGENERATION AND DEGENERATION OF
PERIPHERAL NERVES
PREPARED BY:
Rajnish Singh(93)
Rashi Dewangan(94)
Renuka nag(95)
Rishabh Bhoi(96)

2. REGENERATION
AND
DEGENERATION
OF PERIPHERAL
NERVES
PREPARED BY:
Rajnish Singh(93)
Rashi Dewangan(94)
Renuka nag(95)
Rishabh Bhoi(96)
LATE SMT INDIRA GANDHI MEMORIAL GOVERNMENT MEDICAL COLLEGE, UTTAR
BASTER KANKER

3. WHAT ARE PERIPHERAL NERVES ?

4. PERIPHERAL NERVES
PNS
BUNDLES OF
NERVE
FIBRES(AXONS)

6. PERIPHERAL NERVES

7. PERIPHERAL NERVES

8. PERIPHERAL NERVES

9. PERIPHERAL NERVES

10. PERIPHERAL NERVES

11. PERIPHERAL NERVES

12. PERIPHERAL NERVES

13. PERIPHERAL NERVES

14. PERIPHERAL NERVES

15. CAUSES OF NERVE INJURY

16. NERVE
INJURY
Nerves can be damaged by too much
pressure, by stretching, or by a cut.
nerve injury can affect the brain's
ability to communicate with muscles
and organs.

17. CAUSES
OF NERVE
INJURY

18. Transection
(Through and
through cut)

19. Crushing

20. Ischaemia
(Interference due to
blood supply),
arteriosclerosis

21. injection of toxic
or poisonous
substances into
nerve

22. systemic diseases
such as “diabetes”

23. GRADING OF NERVE INJURY( SUNDARLAND’S
CLASSIFICATION )
First degree injury: Most commonly seen and is secondary to ischaemia caused by direct
pressure to a nerve for limited time.
Ischaemia produces local anoxia( complete lack of O2) with temporary impairment of
nerve function.
It gets corrected within few hours to few weeks, because the axon is not destroyed but
merely loses its functional properties for a short time.

24. GRADING OF NERVE INJURY( SUNDARLAND’S
CLASSIFICATION )
First degree injury:
It is like SLEEPING FOOT
Leads to ischaemia & hypoxia of the vessels that supply nerves ( known as
NERVI VASORUM )

25. GRADING OF NERVE INJURY( SUNDARLAND’S
CLASSIFICATION )
second degree injury: prolonged or severe pressure, damages nerve
fibres at the pressure point finally causing death of axon locally and distally

26. GRADING OF NERVE INJURY( SUNDARLAND’S
CLASSIFICATION )

27. GRADING OF NERVE INJURY( SUNDARLAND’S
CLASSIFICATION )
Third degree injury: endoneurial tubes becoming interrupted.
fourth degree injury: fascicles becoming disorganised

28. GRADING OF NERVE INJURY( SUNDARLAND’S
CLASSIFICATION )
Fifth degree injury: epineurium tubes becoming interrupted.

29. SEDDON’S CLASSIFICATION OF NERVE
INJURY
Neurapraxia: least severe form of injury where nerve is compressed or when
blood supply to the nerve is temporarily disrupted.
usually temporary in
nature and recovery
can be rapid in least
severe forms( within
few hours )

30. SEDDON’S CLASSIFICATION OF NERVE
INJURY
Axonotmesis: axon itself is disrupted and is more severe in nature.
Wallerian degeneration takes place here.

31. SEDDON’S CLASSIFICATION OF NERVE
INJURY
Axonotmesis:
Leads to wallerian degeneration
Repair is possible
Because endometrium is intact
Repair requires about 18 months

32. SEDDON’S CLASSIFICATION OF NERVE
INJURY
Neurotmesis: most severe form of injury in which surrounding
environment( encapsulating connective tissue) along with axon is affected.
Epineurium and
perineurium are
intact
least chance of
recovery

33. DEGENERATION OF PERIPHERAL
NERVES

34. DEGENERATION OF PERIPHERAL NERVES
When a nerve is sectioned, the distal part of the nerve separated from the
cell body degenerates.
Named after Augustus Waller in
1862 after he first described
degenerative changes in distal part
of cut nerve fibre.

35. DEGENERATION OF PERIPHERAL NERVES
degeneration
takes place at
three levels
changes in
distal stump
Changes at
site of injury
Changes in
soma

36. DEGENERATION OF PERIPHERAL NERVES
changes in distal stump
Undergoes complete degeneration, the process starts within 24 hours of
injury.
Changes in action potential observed as early as 2 days after section.
3
rd day: impulse conduction decreases markedly
5
th day: impulses no longer produced.

•Axis cylinder breaks up into short lengths and after a few days little
dust like particles are left in the space formerly occupied by axon

37. DEGENERATION OF PERIPHERAL NERVES
changes in distal stump
•Axis cylinder breaks up into short lengths and after a few days little
dust like particles are left in the space formerly occupied by axon.
•Myelin sheath breaks up,more slowly than the axon Into small oily
droplets. It’s destruction occurs in two stages.
physical destruction: no change in histochemistry of ovoids
Chemical destruction: starts on 8
th day and goes on till 32
nd day. It is
caused by enzymes of Schwann cells.
Macrophages lines the endoneurial tubes.

38. DEGENERATION OF PERIPHERAL NERVES
changes in distal stump

39. DEGENERATION OF PERIPHERAL NERVES
changes in distal stump

•Nucleus of Schwann cell starts multiplying mitotically with formation of
cords of cell which fill up the endoneurial tubes.
•Macrophages from endoneurium start digesting waste of axis cylinder
and of myelin sheath.(due to release of Histamine and serotonin from
endoneurial lining)
•Once the wastes are cleared, Schwann cell cytoplasm starts
proliferating and fills up the endoneurial tubes ( 3 months )

40. DEGENERATION OF PERIPHERAL NERVES
changes at the site of injury
Schwann cell mainly from distal end differentiate into thin elongated
cells.
They can bridge up the gap up to 3 cms.(if the gap is more than 3 cm it is
difficult to fill up, because of inter-lacing of fibres)
Rate of progress of growth is 1-2 mm/day

41. DEGENERATION OF PERIPHERAL NERVES
changes in soma( nerve cell body )
Changes begin within 48 hours of nerve section
and reach to maximum by 15-20 days
Chromatolysis: Nissl’s granules disintegrate
( break up into fine dust) and lose their
staining reaction after 15-20 days and cell
become colourless.
Nucleus zone around the periphery of cell
body.
Nissl substance( RNA ) dissolves(opens) so
that protein can be
manufactured to help the neurone to survive

42. DEGENERATION OF PERIPHERAL NERVES
Degree of damage and chromatolysis depends on :
I)variety of neurons affected
a) At the periphery, changes as described before occurs
b) In the central nervous system (CNS): No regeneration of nerve cell takes
place because it has no centrosomes.
c) In the ANS changes are difficult to demonstrate due to normal
sparseness of Nissl granules.
II) distance of the lesion from nerve cell: if less, more damage.
III) Nature of injury
a) if sharp cut , effects will be less
b) if forcibly torn, death of torn cell occurs.

43. DEGENERATION OF PERIPHERAL NERVES
Degree of damage and chromatolysis depends on :
II) distance of the lesion from nerve cell: if less, more damage.
III) Nature of injury
a) if sharp cut , effects will be less
b) if forcibly torn, death of torn cell occurs.

44. DEGENERATION OF PERIPHERAL NERVES

45. DEGENERATION OF PERIPHERAL NERVES

46. DEGENERATION OF PERIPHERAL NERVES
NOTE: Now if the damage is in the
CNS, no further changes take
place ( because CNS neurons do
not have the growth promoting
chemicals needed for regeneration
and CNS myelin is a potent
inhibitor of axonal growth. But if
the damage is in the PNS,
neurolemma shows the further
changes

47. DEGENERATION OF PERIPHERAL NERVES
Nerve growth factor ( NGF )
NGF are a part of neurotrophins family that include Brain-
derived neurotrophic factor (BDNF),
neurotrophin-3(NT-3) and neurotrophin 4/5 secreted by
distal segment of nerve.
It has multiple functions like:
•Survival of degeneration peripheral nerve cell.
•Nerve growth and regulation( include cell body size,
Axonal terminal sprouting, Dendritic growth )

48. DEGENERATION OF PERIPHERAL NERVES
Nerve growth factor ( NGF )
•Inhibition of neurotransmitter ( cause degenerative
hypersensitivity)
•Has endocrine functions like: catecholamine production in
adrenal medulla, steroid production and spermatogenesis in
the testis.
•In differentiation of granulocyted, monocytes and
lymphocytes.

49. REGENERATION OF
PERIPHERAL
NERVES

50. REGENERATION OF PERIPHERAL NERVES
Criteria for Regeneration
1.Neurilemma should be intact.
2.Nucleus should be intact.
3.Gap should not be more than 3 cms.
4.Cut ends should be in same end line

51. REGENERATION OF PERIPHERAL NERVES

52. REGENERATION OF PERIPHERAL NERVES

53. REGENERATION OF PERIPHERAL NERVES
soma tries to repair the
axon by synthesising
new structural
proteins that fills up
and distends the
cisterns of rough
endoplasmic reticulum.
Also, chromatolysis is
reversible, if the neuron
survive and re-
establishes its contact
with the appropriate
target
Axonal
reaction
Regeneration in
axonal axis
Somatic body
At the site of injury

54. REGENERATION OF PERIPHERAL NERVES
Axonal changes
In proximal stump, Axonal sprouts develop and elongates
and then grows out in all directions as rounded psedopods
like structures called fibrils towards the distal stump.
This results from growth promoting factors secreted by
Schwann’s cell and increased production of neurotrophins
from the denervated distal stump
Sprouts elongate by formation of a growth cone at their
growing ends.

55. REGENERATION OF PERIPHERAL NERVES

56. REGENERATION OF PERIPHERAL NERVES
Axonal changes
The Schwann cells that had survived the degeneration
multiply and form rows along the pathway previously taken
by disintegrated distal axon.
Each axon gives rise to 50-100 fibrils which are guided by
fibers of Schwann cell into the distal ends of endoneurial
tubes.
Out of the many sprouting branches, one branch finds the
way through the Schwann cells and finally reinnervates the
original target structure

57. REGENERATION OF PERIPHERAL NERVES

58. REGENERATION OF PERIPHERAL NERVES
Axonal changes
To begin with, rate of growth is 0.25 mm/day , but once it enters
the distal stump, the rate of growth becomes 3-4 mm/day.
As it grows deeper down, the rate of growth further increases
because mechanical conditions for regeneration are more
suitable than those in a cut nerve end.
In approx. 15 days, Schwann cell filling the endoneurial tube
starts laying down myelin sheath around the successful fibril,
which is completed by one year

59. REGENERATION OF PERIPHERAL NERVES

60. REGENERATION OF PERIPHERAL NERVES
Somatic changes
The somatic regains its size.
The number of Nissl granules slowly reappears.
Other organelles also reappears.
The cell loses excess fluid and regain its normal size.
The nucleus occupies the central position.

61. REGENERATION OF PERIPHERAL NERVES
Changes at site of injury
The neurotransmitter release at Axonal terminal decreases.
Therefore, when a neurotransmitter is released following
regeneration, the response of the target tissue to the
neurotransmitter is increased. This is called denervation
hypersensitivity.

62. REGENERATION OF PERIPHERAL NERVES
overall changes in regeneration
axis cylinder( central axon ) from
proximal stump grows as rounded
pseudopod in fibrils towards distal end.
This result from growth promoting
factors secreted by Schwann cells and
increased production of neurotrophin
from the denervated distal stump.
Each axon give rise to 50-100 fibrils
which are guided by Schwann cells into
distal end.

63. REGENERATION OF PERIPHERAL NERVES
overall changes in regeneration
In approx, 15 days, Schwann cell filling the endometrial tube start
laying down the myelin sheath round the successful fibril, which is
completed by one year.
Once the regenerated axon reaches its target, a new functional
connection( neuromuscular junction) is formed.
Increase in diameter is restricted by size of parental nerve cell.
Therefore functional recovery is not full in mixed nerve unlike motor
or sensory nerve.

64. REGENERATION OF PERIPHERAL NERVES
The recovery nerves is mediated through several processes
The injury results in the activation and retrograde transport of
injury-related signal molecules to the cell soma.
These molecules help the nerve cell to express regeneration-
associated genes(RAGs) , the function of which are to support
nerve growth and elongation as well as axonal guidance.
Several neurotrophic factors including nerve growth factor ( NGF )
are upregulated in the dedifferentiated Schwann cells, which in fact
are growth promoting.
Macrophages and Schwann cells also release transforming growth
factor-ß (TGF-ß).

65. Factors influencing
Regeneration

66. REGENERATION OF PERIPHERAL NERVES
Factors influencing Regeneration
Successful axonal and somatic regeneration depends mainly on four
factors:
Severity of injury
If the gap between the proximal and distal parts is more than 3mm, the
multiple outgrowths intermesh and form a tumour like swelling called
NEUROMA

67. REGENERATION OF PERIPHERAL NERVES
Factors influencing Regeneration

•If neuroma is
formed,
successful
regeneration
can never
occur
•If the
neuroma
involves
sensory fibre,
pain is felt at
the site when
touched.

68. REGENERATION OF PERIPHERAL NERVES
Factors influencing Regeneration
Condition of soma
If the axonal damage is close to cell body, a larger part of neuronal
membrane and cytoplasm is lost. In such situations, the neuron often
dies instead of regeneration

69. REGENERATION OF PERIPHERAL NERVES
Factors influencing Regeneration
Location of injury
In the CNS, a single oligodendroglia sends out many processes to
myelinate several ( around 15 ) axons.
Therefore even though the axonal sprouting occurs, the
oligodendroglia cannot form a path along which the sprouts can grow.
Besides, glial scars formed by astrocytes pose obstruction in the
pathway of the growth cone. Hence, axons in the CNS regenerate less
successfully than axons in the PNS

71. REGENERATION OF PERIPHERAL NERVES
Factors influencing Regeneration
Neurotrophins
When specific neurotrophins are administered to the site of injury, the
growth of the regenerating sprout is enhanced and enmeshing of the
branches does not occur.

72. DEGENERATION OF PERIPHERAL NERVES
FUNCTIONAL ASSESSMENT OF NERVE DAMAGE USING STRENGTH-DURATION CURVE
Relies on varying the strength and
duration of a stimulus applied to nerve
and evaluating the biological response

73. DEGENERATION OF PERIPHERAL NERVES
STRENGTH-
DURATION
CURVE
Relies on varying the strength and
duration of a stimulus applied to nerve
and evaluating the biological response

74. DEGENERATION OF PERIPHERAL NERVES
STRENGTH-DURATION CURVE

75. DEGENERATION OF PERIPHERAL NERVES
STRENGTH-DURATION CURVE

76. DEGENERATION OF PERIPHERAL NERVES
STRENGTH-DURATION CURVE

77. DEGENERATION OF PERIPHERAL NERVES
STRENGTH-DURATION CURVE

78. DEGENERATION OF PERIPHERAL NERVES
STRENGTH-DURATION CURVE
For red curve:
Rheobase: minimum strength of
stimulus that can elicit a biological
response.
Utilization time: it is the duration for
which a stimulus of rheobase
strength needs to be applied in order
to elicit a biological response
Chronaxie: it is the duration that a
stimulus twice the strength of
rheobase needs to be applied in
order to elicit a response

79. DEGENERATION OF PERIPHERAL NERVES
STRENGTH-DURATION CURVE
For blue curve :
Rheobase: increased
Utilization time: increased
Chronaxie: increased

80. REGENERATION OF PERIPHERAL NERVES
In case of CNS
Absence of endoneurial tubes.
No centrosomes in nerve cells
Failure of oligodendrocytes to serve as in the
same manner as Schwann cells in PNS.

81. REGENERATION OF PERIPHERAL NERVES
In case of CNS
Laying down of scar tissue by active
astrocyte cells.
Absence of nerve growth factors.
Production of nerve inhibitory factors in
CNS by myelin
Unlikely to form new synapses

82. TREATMENT FOR NERVE FIBER
DEGENERATION AND REGENERATION
There is no cure for nerve fibre degeneration :( but
there are treatment that can help promote regeneration
and improve function.

83. TREATMENT FOR NERVE FIBER
DEGENERATION AND REGENERATION
Surgery to repair the injured nerve
Physical therapy to help the muscle and nerves
relearn to work together
Occupational therapy to help people learn to perform
activities of daily living
Medications to relieve pain and inflammation

84. In some cases, nerve grafting may be
necessary. Nerve grafting involves
transplanting a healthy nerve from another
part of body to the injured area
Nerve fiber degeneration and
regeneration is a complex process that
can take several months or even years to
complete. With the right treatment, many
people can regain some or all of the
function that they lost due to nerve
damage

85. SUMMARY

86. SUMMARY

87. SUMMARY

88. SUMMARY

89. SUMMARY

90. SUMMARY

91. SUMMARY
Samajh kuch nai aaya
Par sunn ke accha laga !!

93. In 4 rounds
Each round contains 2 questions
Round 1: MCQ
Round 2: True / false
Round 3: fill in the blanks/one word
Round 4: assertion and reasons

94. A “Saturday Night Palsy” or mild compression
injury that recovers spontaneously in 24 hours
would classify as ____________
A.Sunderland grade 4
B.Neurotmesis
C.Axonotmesis
D.Neurapraxia

95. A “Saturday Night Palsy” or mild compression
injury that recovers spontaneously in 24 hours
would classify as ____________
A.Sunderland grade 4
B.Neurotmesis
C.Axonotmesis
D.Neurapraxia

96. Which of the following is a common symptom
of peripheral nerve degeneration ?
A.Increased nerve sensitivity
B.Rapid nerve growth
C.Numbness or tingling
D.Heightened reflexes

97. Which of the following is a common symptom
of peripheral nerve degeneration ?
A.Increased nerve sensitivity
B.Rapid nerve growth
C.Numbness or tingling
D.Heightened reflexes

98. Wallerian degeneration leads to the
complete removal of axons, myelin,
Schwann cells, and basal lamina from the
distal axon
FALSE

99. In nerve injury, if the gap is more than 3
cm it is easy to fill up
FALSE

100. In an injury graded as “axonotmesis” on
the seddon scale, the ____________ will
always remain intact
Epineurium

101. The fibrous middle layer of a peripheral
nerve that contains axons of a similar
type is known as the ________________
Perineurium

103. Assertion: Neurotrophic factors aid in the regeneration of
peripheral nerves.
Reason: neurotrophic factors promote the survival,
growth and dedifferentiation of neurons, thereby
facilitating nerve regeneration after injury
A)both assertion and reason are correct
B)Assertion is correct but reason is false
C)Assertion is false but reason is correct
D)Both assertion and reason are false

104. Assertion: Neurotrophic factors aid in the regeneration of
peripheral nerves.
Reason: neurotrophic factors promote the survival,
growth and dedifferentiation of neurons, thereby
facilitating nerve regeneration after injury
A)both assertion and reason are correct
B)Assertion is correct but reason is false
C)Assertion is false but reason is correct
D)Both assertion and reason are false

105. Assertion: peripheral nerve regeneration occurs at a faster
rate in elderly individuals compared to younger individuals.
Reason: aging can lead to a decline in the regenerative
capacity of peripheral nerves due to reduced growth factor
production and slower cellular processes
A)both assertion and reason are correct
B)Assertion is correct but reason is false
C)Assertion is false but reason is correct
D)Both assertion and reason are false

106. Assertion: peripheral nerve regeneration occurs at a faster
rate in elderly individuals compared to younger individuals.
Reason: aging can lead to a decline in the regenerative
capacity of peripheral nerves due to reduced growth factor
production and slower cellular processes
A)both assertion and reason are correct
B)Assertion is correct but reason is false
C)Assertion is false but reason is correct
D)Both assertion and reason are false

107. BONUS QUESTIONS

109. A patient presents with weakness and numbness in the
wrist and hand following a traumatic injury. Which nerve is
most likely affected?
A)Radial nerve
B)Median nerve
C)Ulnar nerve
D)Musculocutaneous nerve

111. In which of the following would motor neuron cell death,
as a direct consequence of injury, be most pronounced?
A)A grade 1 compression injury to the ventral root resulting from a
herniated disk.
B)A Saturday night palsy injury to the radial nerve in the arm
C)A grade 3 strict injury to the C5 spinal nerve resulting from a bicycle
accident
D)A grade 5 injury to the recurrent branch of the median nerve ( in the
hand) creating a small gap that is successfully surgically repaired
within 24 hours

113. Vishnu, a 55 year old man had an
autonomic neuropathy that disrupted the
sympathetic nerve supply to the pupillary
dilator muscle of his right eye. While having
his eyes examined, the opthalmologist
placed phenylephrine in his eyes. The right
eye became much more dilated than the
left eye. This suggest that

114. A)The sympathetic nerve to the right eye had regenerated
B)The parasympathetic nerve supply to the right eye
remained
C)Phenylephrine blocked the pupillary constrictor muscle of
the right eye.
D)Denervation hypersensitivity had developed
E)The left eye also had nerve damage and so was not
responding as expected .

115. Do you have
any questions??
!

116. Many thanks
for your time