Nerve Regeneration and Rehab

Question 1

What are the three main causes of spinal cord injury?

Answer 1

Acute/ traumatic injury, degenerative disease with loss of neurons, loss of myelin

Question 2

Which brain is Tau protein found in…Alzheimer’s Brain or TBI Brain?

Answer 2

They are found in a TBI brain….you can see changes in mood, depression and cognitive problems

Question 3

What is a main barrier to the repair of a damaged nervous system?

Answer 3

Repair is limited because of the loss of neurons in either the CNS or PNS acts as a barrier to repair

Question 4

What are the requirements for effective nerve regeneration?

Answer 4

1- Survival of the nerve cell body

2- Clearance of the damaged distal axon, myelin breakdown products and other tissue debris

3- An environment that stimulates new axonal growth

4- Guidance cues for the axon to find its original cellular target

Question 5

What is epineurium?

Answer 5

Connective tissue sheath that surrounds axons in the peripheral nerve

Question 6

What is perineurium?

Answer 6

Composed of ECM proteins that can promote axon elongation after inury

Question 7

What is wallerian degeneration?

Answer 7

Removal of distal axonal fragments and other damaged tissue

Question 8

How long does wallerian degeneration take in the PNS?

Answer 8

About 1 week

Question 9

What does wallerian degeneration allow Schwann cells to do?

Answer 9

The removal of damaged tissue allows schwann cells to align and guide the growing axon

Question 10

Which nerve damage is easier to repair…..a cut nerve or a compressed nerve?

Answer 10

A compressed nerve is easier to repair because some axons are spared which makes repair and recovery easier to achieve

Question 11

What is the normal function of schwann cells?

Answer 11

They normally myelinate peripheral nerve cells

Question 12

During nerve repair, what is the function of schwann cells?

Answer 12

They differentiate and proliferate to secrete extracellular matrix molecules that stimulate axonal sprouting and elongation

Question 13

Where do growth factors and neutrophins come from? What is their function?

Answer 13

They come from differentiated schwann cells and they promote the survival of the neuronal cell body

Question 14

What are the main reasons that regenerating peripheral nerves can be reconnected with targets?

Answer 14

The guidance cues provided by the bands of Bunger cells and the Ach receptors that remain in the muscle.

Schwann cells guide regenerating axons to line up with the Ach receptors on the muscle.

Question 15

Pre and post injury….how does the axonal innervation of the target muscle compare?

Answer 15

It looks almost exactly identical pre and post

Question 16

Compare the efficacy of nerve repair in the CNS to the PNS?

Answer 16

CNS repair is not every effective as compared to repair in the PNS….even when the nerve cell body survives there is very little success

Question 17

Why is nerve repair not very effective in the CNS?

Answer 17

Because even when the cell body survives, the other three requirements for regeneration are not present in the CNS

Question 18

Does Wallerian degeneration occur in the CNS?

Answer 18

Yes, it actually begins quickly but clearance of myelin debris is slow and incomplete….this leads to impaired nerve regeneration

Question 19

What is a glial scar and where does it typically occur?

Answer 19

A glial scar is a chemical and physical barrier to repair. This typically occurs in the CNS

Question 20

What are glial scars made from?

Answer 20

They are formed by reactive astrocytes and other cells providing and depositing Chondroitin sulfate proteoglycans

Question 21

What are chondroitin sulfate proteoglycans?

Answer 21

Large molecules with a protein core and many glycosamine side chains

Question 22

Do axons like proteoglycans?

Answer 22

No! Not at all….the growth cone will retreat in the presence of proteoglycans

Question 23

What are 5 strategies to repair the damaged nervous system?

Answer 23

1- Biomaterials to provide a growth promoting substance for growing axons

2- Growth factor targets to promote neuronal survival and axonal sprouting

3- Agents that will change the local environment in the lesion to promote axonal regrowth

4- Agents to promote remyelination after injury

5- Cell replacement therapy to replace neurons or oligodendrocytes

Question 24

What is the role of grafts in nerve damage repair?

Answer 24

Can be used either in the PNS or the CNS to promote repair. It provides a source of growth factors to stimulate axonal regeneration and neuronal survival and permissive substrate

Question 25

What is chondroitinase treatment?

Answer 25

Condroitinase ABC is an enzyme that can remove sugar side chains from inhibitory proteoglycans that are expressed in the glial scar

Question 26

What are the different types of side chains?

Answer 26

Embryonic (pluripotent), Adult (multipotent), neural (committed but multipotent), reprogrammed cells from other tissues

Question 27

What needs to happen for a stem cell to successfully restore function?

Answer 27

1- differentiate into the appropriate kind of neuron

2- make connections with the appropriate target cells

3- form working synapses