Week 8 Part 1 Flashcards
What are causes of peripheral nerve injury?
Trauma Compression Metabolic disorders Inflammation Tumours Frostbites
What are examples of mechanical nerve injuries?
Crush and compression
Laceration
Stretch
Physiological healing processes
What are the structures of peripheral nerves?
Endoneurium
Perineurium
Epineurium
Fascicles
What is endoneurium?
A layer of connective tissue that surrounds axons
What is perineurium?
A protective sheath covering nerve fascicles
What is epineurium?
The outermost layer of dense, irregular connective tissue surrounding a peripheral nerve
What is fascicles?
A small bundle of nerve fibres enclosed by perineurium
What is the classification of peripheral nerve injury?
Neurapraxia
Axonotmesis
Neurotmesis
What is Neurapraxia?
Temporary interruption of conduction without loss of axonal continuity
What is Axonotmesis?
Loss of relative continuity of axon and its myelin sheath
The preservation of connective tissue framework of the nerve
What is Neurotmesis?
Total tranafection of the nerve
What is the classification of PNI (Sunderland)
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
What is the pathology and prognosis of neurapraxia?
Pathology: myelin injury/ischemia
Prognosis: excellent recovery in weeks to months
What is the pathology and prognosis of axonotmesis?
Pathology: axon loss and variable strolls disruption
Prognosis: good to poor, depending upon integrity of supporting structures and distance to targets
What is the pathology and prognosis of Neurotmesis?
Pathology: axon loss, endoneurial tubes severed, perineurium severed, epineurium severed
Prognosis: no spontaneous recovery, surgery required
What is wallerian degeneration?
The process of degeneration of the axon distal to a site of transection
What is a normal condition of Wallerian degeneration?
An intact axon with myelinating Schwann cells and scattered fibroblasts
What does injury produce?
Tissue damage at the lesion
Macrophages accumulate at the lesion site within 24hr after injury
Where does macrophages come from?
White blood cells
Where does microglia macrophage come from?
CNS
What does degeneration produce?
Lots of debris
What does Schwann cells myelin become?
galactin-3 positive
What happens when there is an injury?
Schwann cells undergo autophagy
What happens after injury?
Myelin is fragmented
Results in down cellular signalling pathway
After injury, what is the first part of repair of body?
Formation of bands of bungera
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
Where does multiple sprouts arise?
Proximal axons
Cross the gap through Schwann cell tubes
Enter distal segment
What happens after axon has gone through debris?
There is extension and re-myelination
Axons grow and reach the end organ
What are new axons myelinated by?
Schwann cells
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
What does regenerating axons form?
Many sprouts
Intact Schwann tube
Schwann cell Basal Lamina
Increased proteoglycans in the endoneurium
Axons can regenerate easily within the Schwann tubes
Disrupted Schwann tube
Schwann cell Basal Lamina discontinuous
Increased proteoglycan within Schwann tubes
Axons cannot regenerate easily because the Schwann tubes are disrupted
What is found within the nerve?
Elasticity
What is close to the injury?
Target tissue
What does large gaps of severed peripheral nerves require?
Insertion of a bridging material
Segment of a nerve
What is sural nerve?
Sensory nerve which isn’t used as much
How else can gaps span?
Suturing a polymeric tube (tubulization)
Why is sural nerve good?
It has all the Schwann cells
What is the purpose of sural nerve?
Provide a conduit consisting of a Basal Lamina scaffold together with their corresponding Schwann cells
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
What is nerve allotransplantation?
Transplantation of a nerve to a receiver from a donor of the same species
Where can donor nerves come from?
Amputated limbs
How can you avoid immuno rejection?
The cells in the non-autologous tissue must be completely eliminated
How can extracellular matrix be preserved?
Thermal, radiation and chemical treatments to remove the cells
What does bio artificial grafts have?
Lower success rates than autologous grafts
What does Allografts have?
Extracellular matrix which is hollow
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
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
Nerve allografts work (months)
The processed nerve allograft remodels into patients own tissue as the axons continue to move toward their distal end targets
Allografts work (years)
Within the remodelled scaffold, the axons finish their maturation process
What are ideal properties of artificial nerve conduits?
- Biocompatibility
- Degradation/ porosity
- Various physical properties
- Protein modification/release
- Physical fit
- Support cells
Biocompatibility
Material should not harm the surrounding tissues
Degradation/porosity
Degradation rate should complement nerve regeneration rate
Various physical properties
An internal scaffold or film should provide directional guidance
Protein modification/release
Laminin/fibronectin coating for increased cellular adhesion, controlled/sustained growth factor release
Physical fit
Conduit should have a large enough internal diameter to not squeeze the regenerating nerve
Wall thickness limited
Support cells
Schwann cells/stem cells capable of delivering neurotrophic factors to site of regeneration
What are materials for artificial nerve conduits?
Biopolymers
Synthetic polymers
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
Synthetic polymers
Cheap, less biocompatible
Polycaprolactone, polyurethane, polyhydroxybutyrate
Tailored degradation and control of mechanical strength, porosity and microstructure properties
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
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
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
How can you repair peripheral nerve?
Schwann cell-seeded sheets
What are problems associated with nerve regeneration?
Regeneration failure due to large gap (>3cm)
Misconnection
Traumatic neuroma
What are the catergories of traumatic neuroma?
Spindle
Lateral or terminal
Spindle neuroma
Internal, focal, fusiform swellings secondary to chronic friction or irritation to a non-disrupted, injured but intact nerve trunk
Lateral or terminal neuroma
Severe trauma with disruption or total transfection of a nerve
What is the occurrence of traumatic neuroma?
1-12 months after injury
Vary in size with no malignant potential
What is gene therapy
Manipulate gene expression of injured neurons
- Promote axonal growth
- 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
What is cell therapy?
Seed the conduits
Genetically modified to secrete neurotrophic factors or growth promoting molecules
What are examples of stem cells?
Bone marrow
Adipose tissue
Dental pulp
What are the sources of cells for grafting?
Schwann cells
Skin-derived Schwann cells
