Damage and Repair in the CNS

Question 1

Give 4 examples of damage in the CNS

What is a common feature of them all?

Answer 1

SCI, TBI, stroke, brain cancer

severe detrimental effects

Question 2

True or False? CNS neurones can regenerate

Answer 2

False

Question 3

What are the 4 thing that prevent regeneration in the CNS?

Answer 3

inhibitory environment
injury response
loss of cells
loss of trophic support

Question 4

Explain the process by which the CNS is damaged starting with the breaking of the BBB

Answer 4

BBB broken
inflammatory cells enter
interact with astrocytes
astrocytes proliferate
reconnect the BBB (dystrophin neurones)

Question 5

What is scarring in the CNS associated with?

Answer 5

up-regulatory molecules and deposition of extracellular matrix

Question 6

Explain how differences in the myelinating cells in the CNS and PNS result in differences in regeneration

Answer 6

In PNS schwann cells lines up to allow axons to reinnervate

In CNS oligodendrocytes do not form guidance path for sprouting axons and express inhibitory molecules

Question 7

How to astrocytes contribute to the CNS’s inability to regenerate? Which molecules are involved?

Answer 7

release factors that promote scar deposition

release inhibitory molecules (proteoglycans)

Question 8

True or False? CNS axons have an intrinsic capacity for regeneration

Answer 8

True, it is just the environment that inhibits regeneration in the CNS

Question 9

What are the 5 components of the inhibitory environment that prevents CNS regeneration?

Answer 9

lack of neurotrophic stimulation
neuronal death
demyelination
glial scar
inhibitory molecules

Question 10

What inhibitory molecules are associated with the glial scar?
What inhibitory molecules are associated with damaged myelin?

Answer 10

• proteoglycans e.g. CSPG

- Nogo, MAG, Omgp

Question 11

Which organ is often used to assess capacity to regenerate and to test drug therapies? Why/

Answer 11

Eyes and the optic nerve
Signals in one direction, cell bodies in retina
Add therapy to vitrius of eye

Question 12

Give examples of some strategies for repair. Hint: They target the areas that make for an inhibitory environment

Answer 12

Inhibitors - antibodies against Nogo
Endogenous stem cells - neurogenesis
Cell therapy - replace dead cells, create favourable environment, bridge cavities, autologous stem cells

Question 13

Which inhibitory molecules would be the most useful to inhibit and why?

Answer 13

RhoA because it is a common pathway for many inhibitory molecules