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Repair And Regeneration > Week 8 Part 1 > Flashcards

Week 8 Part 1 Flashcards

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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
After injury, what is the first part of repair of body?
Formation of bands of bungera
26
What does Schwann cells do?
Proliferate and align up to form bands of Bungner | Then forms endoneurial tubes with the remaining connective tissue basement membrane
27
Where does multiple sprouts arise?
Proximal axons Cross the gap through Schwann cell tubes Enter distal segment
28
What happens after axon has gone through debris?
There is extension and re-myelination | Axons grow and reach the end organ
29
What are new axons myelinated by?
Schwann cells
30
What are the 4 steps of peripheral nerve regeneration?
(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
What does regenerating axons form?
Many sprouts
32
Intact Schwann tube
Schwann cell Basal Lamina Increased proteoglycans in the endoneurium Axons can regenerate easily within the Schwann tubes
33
Disrupted Schwann tube
Schwann cell Basal Lamina discontinuous Increased proteoglycan within Schwann tubes Axons cannot regenerate easily because the Schwann tubes are disrupted
34
What is found within the nerve?
Elasticity
35
What is close to the injury?
Target tissue
36
What does large gaps of severed peripheral nerves require?
Insertion of a bridging material | Segment of a nerve
37
What is sural nerve?
Sensory nerve which isn’t used as much
38
How else can gaps span?
Suturing a polymeric tube (tubulization)
39
Why is sural nerve good?
It has all the Schwann cells
40
What is the purpose of sural nerve?
Provide a conduit consisting of a Basal Lamina scaffold together with their corresponding Schwann cells
41
What are problems of autologous nerve grafts?
Potential neuroma formation at the donor site Frequent disappointing functional outcomes Donor nerves are often of small caliber and limited in number
42
What is nerve allotransplantation?
Transplantation of a nerve to a receiver from a donor of the same species
43
Where can donor nerves come from?
Amputated limbs
44
How can you avoid immuno rejection?
The cells in the non-autologous tissue must be completely eliminated
45
How can extracellular matrix be preserved?
Thermal, radiation and chemical treatments to remove the cells
46
What does bio artificial grafts have?
Lower success rates than autologous grafts
47
What does Allografts have?
Extracellular matrix which is hollow
48
How does processed nerve allografts work (hours)?
When implanted, the body begins to revascularise and repopulate the extracellular matrix of the processed nerve allograft with cells
49
Nerve allografts works (days)
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
Nerve allografts work (months)
The processed nerve allograft remodels into patients own tissue as the axons continue to move toward their distal end targets
51
Allografts work (years)
Within the remodelled scaffold, the axons finish their maturation process
52
What are ideal properties of artificial nerve conduits?
1. Biocompatibility 2. Degradation/ porosity 3. Various physical properties 4. Protein modification/release 5. Physical fit 6. Support cells
53
Biocompatibility
Material should not harm the surrounding tissues
54
Degradation/porosity
Degradation rate should complement nerve regeneration rate
55
Various physical properties
An internal scaffold or film should provide directional guidance
56
Protein modification/release
Laminin/fibronectin coating for increased cellular adhesion, controlled/sustained growth factor release
57
Physical fit
Conduit should have a large enough internal diameter to not squeeze the regenerating nerve Wall thickness limited
58
Support cells
Schwann cells/stem cells capable of delivering neurotrophic factors to site of regeneration
59
What are materials for artificial nerve conduits?
Biopolymers | Synthetic polymers
60
Biopolymers
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
Synthetic polymers
Cheap, less biocompatible Polycaprolactone, polyurethane, polyhydroxybutyrate Tailored degradation and control of mechanical strength, porosity and microstructure properties
62
What are the forms of luminal fillers of polymer nerve conduit?
``` Gel rod Gel layer Electro-spun fibre layer Microsphere-embedded layer Sponge Electro-spun fibre mat roll Aligned filaments ```
63
What are the structures of synthetic nerve conduits?
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
Controlled release of neurotrophic factors
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
How can you repair peripheral nerve?
Schwann cell-seeded sheets
66
What are problems associated with nerve regeneration?
Regeneration failure due to large gap (>3cm) Misconnection Traumatic neuroma
67
What are the catergories of traumatic neuroma?
Spindle | Lateral or terminal
68
Spindle neuroma
Internal, focal, fusiform swellings secondary to chronic friction or irritation to a non-disrupted, injured but intact nerve trunk
69
Lateral or terminal neuroma
Severe trauma with disruption or total transfection of a nerve
70
What is the occurrence of traumatic neuroma?
1-12 months after injury | Vary in size with no malignant potential
71
What is gene therapy
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
What is cell therapy?
Seed the conduits | Genetically modified to secrete neurotrophic factors or growth promoting molecules
73
What are examples of stem cells?
Bone marrow Adipose tissue Dental pulp
74
What are the sources of cells for grafting?
Schwann cells | Skin-derived Schwann cells

Repair And Regeneration (16 decks)

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