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Repair And Regeneration > Week 8 Part 1 > Flashcards

Week 8 Part 1 Flashcards

1
Q

What are causes of peripheral nerve injury?

A 
Trauma
Compression
Metabolic disorders
Inflammation
Tumours 
Frostbites
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2
Q

What are examples of mechanical nerve injuries?

A

Crush and compression
Laceration
Stretch
Physiological healing processes

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3
Q

What are the structures of peripheral nerves?

A

Endoneurium
Perineurium
Epineurium
Fascicles

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4
Q

What is endoneurium?

A

A layer of connective tissue that surrounds axons

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5
Q

What is perineurium?

A

A protective sheath covering nerve fascicles

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6
Q

What is epineurium?

A

The outermost layer of dense, irregular connective tissue surrounding a peripheral nerve

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7
Q

What is fascicles?

A

A small bundle of nerve fibres enclosed by perineurium

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8
Q

What is the classification of peripheral nerve injury?

A

Neurapraxia
Axonotmesis
Neurotmesis

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9
Q

What is Neurapraxia?

A

Temporary interruption of conduction without loss of axonal continuity

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10
Q

What is Axonotmesis?

A

Loss of relative continuity of axon and its myelin sheath

The preservation of connective tissue framework of the nerve

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11
Q

What is Neurotmesis?

A

Total tranafection of the nerve

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12
Q

What is the classification of PNI (Sunderland)

A

1st: temporary malfunction in a portion of the axon
2nd: severance of the axon
3rd: the loss of endoneurium
4th: the loss of perineurium
5th: complete nerve transection

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13
Q

What is the pathology and prognosis of neurapraxia?

A

Pathology: myelin injury/ischemia
Prognosis: excellent recovery in weeks to months

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14
Q

What is the pathology and prognosis of axonotmesis?

A

Pathology: axon loss and variable strolls disruption
Prognosis: good to poor, depending upon integrity of supporting structures and distance to targets

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15
Q

What is the pathology and prognosis of Neurotmesis?

A

Pathology: axon loss, endoneurial tubes severed, perineurium severed, epineurium severed
Prognosis: no spontaneous recovery, surgery required

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16
Q

What is wallerian degeneration?

A

The process of degeneration of the axon distal to a site of transection

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17
Q

What is a normal condition of Wallerian degeneration?

A

An intact axon with myelinating Schwann cells and scattered fibroblasts

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18
Q

What does injury produce?

A

Tissue damage at the lesion

Macrophages accumulate at the lesion site within 24hr after injury

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19
Q

Where does macrophages come from?

A

White blood cells

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20
Q

Where does microglia macrophage come from?

A

CNS

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21
Q

What does degeneration produce?

A

Lots of debris

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22
Q

What does Schwann cells myelin become?

A

galactin-3 positive

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23
Q

What happens when there is an injury?

A

Schwann cells undergo autophagy

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24
Q

What happens after injury?

A

Myelin is fragmented

Results in down cellular signalling pathway

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25
Q

After injury, what is the first part of repair of body?

A

Formation of bands of bungera

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26
Q

What does Schwann cells do?

A

Proliferate and align up to form bands of Bungner

Then forms endoneurial tubes with the remaining connective tissue basement membrane

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27
Q

Where does multiple sprouts arise?

A

Proximal axons
Cross the gap through Schwann cell tubes
Enter distal segment

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28
Q

What happens after axon has gone through debris?

A

There is extension and re-myelination

Axons grow and reach the end organ

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29
Q

What are new axons myelinated by?

A

Schwann cells

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30
Q

What are the 4 steps of peripheral nerve regeneration?

A

(A) - axon becomes fragmented at injury site
(B) - macrophages clean off the dead axon distal to the injury
(C) - axon sprout or filaments grow through a regeneration tube formed by Schwann cells
(D) - axon regenerated and a new myelin sheath forms

31
Q

What does regenerating axons form?

A

Many sprouts

32
Q

Intact Schwann tube

A

Schwann cell Basal Lamina
Increased proteoglycans in the endoneurium
Axons can regenerate easily within the Schwann tubes

33
Q

Disrupted Schwann tube

A

Schwann cell Basal Lamina discontinuous
Increased proteoglycan within Schwann tubes
Axons cannot regenerate easily because the Schwann tubes are disrupted

34
Q

What is found within the nerve?

A

Elasticity

35
Q

What is close to the injury?

A

Target tissue

36
Q

What does large gaps of severed peripheral nerves require?

A

Insertion of a bridging material

Segment of a nerve

37
Q

What is sural nerve?

A

Sensory nerve which isn’t used as much

38
Q

How else can gaps span?

A

Suturing a polymeric tube (tubulization)

39
Q

Why is sural nerve good?

A

It has all the Schwann cells

40
Q

What is the purpose of sural nerve?

A

Provide a conduit consisting of a Basal Lamina scaffold together with their corresponding Schwann cells

41
Q

What are problems of autologous nerve grafts?

A

Potential neuroma formation at the donor site
Frequent disappointing functional outcomes
Donor nerves are often of small caliber and limited in number

42
Q

What is nerve allotransplantation?

A

Transplantation of a nerve to a receiver from a donor of the same species

43
Q

Where can donor nerves come from?

A

Amputated limbs

44
Q

How can you avoid immuno rejection?

A

The cells in the non-autologous tissue must be completely eliminated

45
Q

How can extracellular matrix be preserved?

A

Thermal, radiation and chemical treatments to remove the cells

46
Q

What does bio artificial grafts have?

A

Lower success rates than autologous grafts

47
Q

What does Allografts have?

A

Extracellular matrix which is hollow

48
Q

How does processed nerve allografts work (hours)?

A

When implanted, the body begins to revascularise and repopulate the extracellular matrix of the processed nerve allograft with cells

49
Q

Nerve allografts works (days)

A

Axons begin to cross the ECM scaffold of the processed nerve allograft toward distal nerve stump. The advancing axons become re-myelinated by Schwann cells

50
Q

Nerve allografts work (months)

A

The processed nerve allograft remodels into patients own tissue as the axons continue to move toward their distal end targets

51
Q

Allografts work (years)

A

Within the remodelled scaffold, the axons finish their maturation process

52
Q

What are ideal properties of artificial nerve conduits?

A
  1. Biocompatibility
  2. Degradation/ porosity
  3. Various physical properties
  4. Protein modification/release
  5. Physical fit
  6. Support cells
53
Q

Biocompatibility

A

Material should not harm the surrounding tissues

54
Q

Degradation/porosity

A

Degradation rate should complement nerve regeneration rate

55
Q

Various physical properties

A

An internal scaffold or film should provide directional guidance

56
Q

Protein modification/release

A

Laminin/fibronectin coating for increased cellular adhesion, controlled/sustained growth factor release

57
Q

Physical fit

A

Conduit should have a large enough internal diameter to not squeeze the regenerating nerve
Wall thickness limited

58
Q

Support cells

A

Schwann cells/stem cells capable of delivering neurotrophic factors to site of regeneration

59
Q

What are materials for artificial nerve conduits?

A

Biopolymers

Synthetic polymers

60
Q

Biopolymers

A

More biocompatible
1. Polysaccharide - agarose, chitosan, alginate
2. Proteins - collagen, genetin, keratin, silk, laminin, fibrin
Tailored mechanical properties and degradation profiles
Encapsulate and present growth factors and ECM proteins to proximal nerve ends

61
Q

Synthetic polymers

A

Cheap, less biocompatible
Polycaprolactone, polyurethane, polyhydroxybutyrate
Tailored degradation and control of mechanical strength, porosity and microstructure properties

62
Q

What are the forms of luminal fillers of polymer nerve conduit?

A 
Gel rod
Gel layer 
Electro-spun fibre layer 
Microsphere-embedded layer 
Sponge 
Electro-spun fibre mat roll 
Aligned filaments
63
Q

What are the structures of synthetic nerve conduits?

A

Basic NC design with void lumen
Multichannel
Inner NC wall surface furnished with nanofibers
Array of nanofibres
Gel of extracellular matrix of other materials

64
Q

Controlled release of neurotrophic factors

A

Embedded in nerve conduit wall
Embedded in polymeric coatings of nerve conduit wall
Encapsulated in biodegradable microspheres embedded in conduit wall
Embedded in extracellular matrix material in lumen
Entrapped in biodegradable nanofibres that are mounted on NC wall

65
Q

How can you repair peripheral nerve?

A

Schwann cell-seeded sheets

66
Q

What are problems associated with nerve regeneration?

A

Regeneration failure due to large gap (>3cm)
Misconnection
Traumatic neuroma

67
Q

What are the catergories of traumatic neuroma?

A

Spindle

Lateral or terminal

68
Q

Spindle neuroma

A

Internal, focal, fusiform swellings secondary to chronic friction or irritation to a non-disrupted, injured but intact nerve trunk

69
Q

Lateral or terminal neuroma

A

Severe trauma with disruption or total transfection of a nerve

70
Q

What is the occurrence of traumatic neuroma?

A

1-12 months after injury

Vary in size with no malignant potential

71
Q

What is gene therapy

A

Manipulate gene expression of injured neurons

  1. Promote axonal growth
  2. Assist regenerating axons to reach their right targets

Genetically modify cells for grating to promote their survival, migration, myelination and to support for axonal growth

72
Q

What is cell therapy?

A

Seed the conduits

Genetically modified to secrete neurotrophic factors or growth promoting molecules

73
Q

What are examples of stem cells?

A

Bone marrow
Adipose tissue
Dental pulp

74
Q

What are the sources of cells for grafting?

A

Schwann cells

Skin-derived Schwann cells

Repair And Regeneration (16 decks)

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