L17 - Regeneration in the Mature Nervous System

Question 1

Why is regeneration important?

Answer 1

Large number of traumatic injuries in peripheral nerves
Spinal cord injury 
Traumatic brain injury 
Stroke 
Loss of neurones in disease

Question 2

Regeneration in Xenopus

Answer 2

Tadpole tail regeneration triggered by BMP’s

Critical period where regeneration can occur

Question 3

Regeneration in Salamander

Answer 3

Schwann cells migrate to the blastoma and help with regrowth

Question 4

Regeneration in Worm

Answer 4

Can regrow whole anterior and posterior regions

Question 5

Nerve structure

Answer 5

Axon surrounded by myelin sheath made of Schwann cells

These form into a fascicle surrounded by endoneurium and perineurium

Question 6

Nerve injuries - axonotmesis

Answer 6

Axon divided but connective tissue layers maintained

Question 7

Nerve injuries - neurotmesis

Answer 7

Axon and connective tissue layers divided

Question 8

Peripheral nerve regeneration

Answer 8

Cell death more likely closer to soma
Proximal axon and soma – reorganisation and re-expression of immature features
- E.g. tubulins
Distal axon – Wallerian degeneration

Question 9

Denervated muscle

Answer 9

Muscle atrophy
AChR reversal to embryonic
MUSK increase
External electrical input can help prevent atrophy

Question 10

What does regeneration involve?

Answer 10

Mitosis and rearrangement of Schwann cells
Formation of Bands of Bungner - rows of Schwann cells to guide axon
Re-growth along dividing Schwann cells
Sprouting – neighbouring cells help reverse damage

Question 11

What is disrupted in crush injuries?

Answer 11

Basal lamina and ECM intact

- Better regrowth and accuracy

Question 12

What is disrupted in cut injuries?

Answer 12

Basal lamina and ECM disrupted

Question 13

Regeneration in CNS

Answer 13

Spinal cord injuries
Regeneration in the brain
Transplants and stem cell

Question 14

Spinal cord injuries

Answer 14

Sprouting followed by failed regeneration and degeneration
Cysts and glial scars form
Recovery of connections difficult

Question 15

Inhibitory myelin

Answer 15

CNS neurons avoid oligodendrocytes in vitro Removing myelin / oligos improves regeneration
Autoimmunisation to myelin proteins ↑ regeneration

Question 16

Name of myelin protein that inhibits axon growth?

Answer 16

Nogo-a

Question 17

Nogo family

Answer 17

Nogoa - 200kd - oligodensrocytes and developing neurons
Nogob - 55kd - many cells
Nogoc - 25kd - muscle

Question 18

Fish and salamanders lack?

Answer 18

Nogo-a

Question 19

Nogo knockout?

Answer 19

Partially decreases inhibition

Question 20

Antibodies against nogo?

Answer 20

Improves regeneration in spinal cord

Question 21

Motor recovery

Answer 21

Partial lesions fairly recoverable - associated with sprouting of remaining fibres
In humans takes several months
Nogo –a suppression improves recovery in rat models

Question 22

Objections to NOGO

Answer 22

No correlation between nogo / receptor level and regenerative capacity
Transplanted hippocampal neurons grow axons into myelin
Much myelin is removed by macrophages after damage
Regeneration is poor in grey matter too

Question 23

Astrocytes

Answer 23

Responsible for poor regeneration

Found in CNS not PNS

Question 24

Astrocytes proliferate at lesions

Answer 24

Glial scar
Jumbled astrocytes
Attachment to astrocytes impairs regeneration
Secrete inhibitory condroitin sulphate proteoglycan - CSPG’s

Question 25

Repair - spinal cord bridges

Answer 25

Biological and artificial

Filled with growth factors, ECM, synthetic matrix

Question 26

Repair - transplant foetal cells

Answer 26

Parkinson’s
- Undesired side-effects
- New trial promising with better defined material
Huntington’s
- Graft survival but little integration or improvement

Question 27

Repair - transplant

Answer 27

Human embryonic stem cell derived progenitors - preparing clinical trial for Parkinson’s
Umbilical cells
Autologous NS stem cells

Question 28

Stem cell dividing neural precursors found in?

Answer 28

Adult vertebrate brain

Fish and amphibia retina

Question 29

Example of regeneration

Answer 29

Male songbirds
- SVZ → High vocal centre

Mammalian forebrain SVZ and dentate gyrus
- Hippocampus and olfactory epithelium

Question 30

Olfactory ensheating cells

Answer 30

Wrap olfactory axon bundles

Early reports - spinal cord regeneration not consistent

Question 31

Mixtures of OEC’s with basal cells can?

Answer 31

Produce new neurons