24 Injury and repair of nervous system

Question 1

What is the main difference in the damage of a peripheral nerve and the damage of an optic nerve?

Answer 1

Peripheral nerve = PNS, good regeneration and functional recovery.

Optic nerve = CNS, limited regeneration and poor recovery

Question 2

State the flow of events when there is PNS injury.

Answer 2

1. Region of axon distal to injury site degenerates but the cell body and proximal axon survive
2. Macrophages clear away degenerating axonal and myelin debris (needs fast action)
3. Tip of proximal axon forms a growth cone that actively elongates the axon
4. Schwann cells form channels and secrete neurotrophic factors to guide generating axons, leading to survival of other parts of the neuron

Question 3

State the flow of events when there is CNS injury.

Answer 3

1. Clearance of degenerating axonal and myelin debris at the injury site is slow and incomplete
2. Activated astrocytes increase in number and size to form a scar (gliosis)
3. Inhibitory factors associated with oligodendrocyte myelin and astrocytes suppress axonal growth
4. Microglia secrete neurotoxic factors that could induce neuronal death

Question 4

What do Schwann cells secrete?

Answer 4

Neurotrophic factors

Question 5

How do astrocytes react when injured?

Answer 5

hypertrophied, inhibit molecules of glial scar e.g. chondroitin sulphate proteoglycans

Question 6

List the inhibitory factors that the oligodendrocytes secrete.

Answer 6

1. Nogo

2. myelin-associated glycoprotein

Question 7

What are the growth inhibitors that bind to receptors on the axonal membrane in axonal injury?
How do they work?

Answer 7

Myelin inhibitors:
- Nogo-A, OMgo, MAG

Astrocyte inhibitors:
- CSPG

Regeneration requires cytoskeleton synthesis and maintenance, which is to be moved into axon membrane, inhibitory factors affect this point to stop axonal regeneration

Question 8

List the strategies to promote CNS regeneration.

Answer 8

1. Replacing CNS environment with a favourable one :
   a. transplantation of peripheral nerve segments
   b. transplantation of immature CNS tissue
   c. transplantation of olfactory nerve ensheathing cells
   d. stem cell transplantation
2. Modify CNS glial environment
   a. neutralizing activity of inhibitory factors from oligodendrocytes by antibodies
   b. inactivation of proteoglycans (from astrocytes) by enzymatic degeneration
   c. suppressing microglial activity

Question 9

Which of the following is false?
To promote CNS regeneration,
A. peripheral nerve graft apposed to the cut end of optic nerve (CNS) to stimulate axonal regeneration of retinal ganglion cells
B. There is continuous formation/growth of olfactory mucosa axons to the olfactory bulb all the time due to the presence of glial cells wrapping around the olfactory nerves
C. Stem cell transplantation is commonly used in Parkinson’s disease, Huntington’s disease
D. Stem cell transplantation is from bone marrow

Answer 9

C.

Transplantation of immature CNS tissue: Parkinson’s disease, Huntington’s disease