L28 - 30 - Injury to NS

Question 1

Henry Head’s peripheral nerve regen. exp - He cut nerves and general sensation and movement returned except?

Answer 1

Incomplete recovery of light touch, temp, pinpricks, 2-point discrimination, fire motor control

Question 2

Wallerian Degen

• What is it?
• 2 weeks post injury
• 3 Weeks post injury
• 3 Months post injury

Answer 2

Degen of axon and myelin sheath below injury site
2 weeks: Nucleus becomes peripheral and nissl substance is lost via chromolysis
3 weeks: Schwann cells proliferate, forming a compact cord, growing axons penetrate schwann cell cord
3 Months: successful regen and restoration of elec activity

Question 3

Neuroma

Answer 3

Occurs during unsuccessful regen where growing axons don’t kinne up with schwann cell cord

Question 4

GAP43 (Growth Associated Protein 43)

Answer 4

Found in growth cones

Question 5

Integrins

Answer 5

Binds to ECM to promote growth

Question 6

In skeletal muscle denervation, NMJ synaptic sites remain intact for weeks - however can also be less accurate

Answer 6

In skeletal muscle denervation, NMJ synaptic sites remain intact for weeks - however can also be less accurate

Question 7

Is crush or cut injury good for regrowth?

Answer 7

Crush = good regrowth
Cut = variable

Question 8

Microsurgery

Answer 8

Reattach proximal and distal stumps or insert nerve graft

Question 9

Regeneration of peripheral nerves is faster with exercise

Answer 9

Regeneration of peripheral nerves is faster with exercise

Question 10

Tau deposition is found in

Answer 10

Alzhemiers diseased brains

Question 11

3 major classes of glia in CNS that react to tissue damage

Answer 11

Astrocyte, oligodendrocytes, microglia

Question 12

Astrocytic Gliosiis

Answer 12

• Upregulate astrocyte cytoskeletal proteins e.g. GFAP (Glial fibrillary acidic protein)
• Upregulate expression of developmental axon guidance molecules
• Hypertrophic
• Proliferate
• Secretes cytokines and GF
• Interdigitate processes
• Secrete ECM e.g. CSPG (chondroitin sulphite proteoglycans)

Question 13

How can upregulating axon guidance molecules via astrocytic gliosis be bad?

Answer 13

In development, they are expressed in certain channels by repulsing axons that touch it so they get bumped into the right direction. In adults, there is no path for them to follow, so when an axon hits it, it just stops or retracts. This leads to Glial Scar formation

Question 14

Glial Scar Formation

Answer 14

Forms a barrier between undamaged tissue and injuy site

Question 15

Nogo, MAG - what are they and what do they bind to

Answer 15

Inhibitory molecules in myelin debris

Binds to Nogo receptor (NgR)

Question 16

Signalling of Nogo receptor activation is done via? It associates with?

Answer 16

Rho A activation -> ROCK -> cytoskeleton -> neurite inhibitions

Associates with p75/LINGO or TROY/LINGO

Question 17

Eph/ephrins, semaphorins, tenascin- what are they?

Answer 17

Axon guidance molecules

Question 18

GFAP (Glial fibrillary acidic protein)

Answer 18

Astrocyte cytoskeletal protein

Question 19

CSPG (chondroitin sulphite proteoglycans) and Collagen IV

Answer 19

Astroctye ECM

Question 20

TGFB (transforming growth factor B) activates astrocytes, what happens when you block it?

Answer 20

Nothing - it doesn’t aid in regeneration

Question 21

Increase/decrease regen:

• Astrocyte ECM inhibition
• GFAP.Vimatin double KO
• Astrocyte ablation
• Blocking Eph A4 (activates Rho)

Answer 21

All increases

Question 22

Nogo and Rho inhibition - amount of regen?

Answer 22

Some

Question 23

Location of neurogenic regions that make stem cells

Answer 23

SVZ and SGZ

1) Subventricular zone of lateral ventricle (goes to olfactory bulb via rostral migratatory stream)
2) Subgranular zone of dentate gyrus of hippocampus (goes to GL layer of hippocamppus)

Question 24

EPO

Answer 24

Increases neurogenesis in brain

Question 25

Inflammatory soup

Answer 25

cytokines, chemokines, metalloproteases

*Chemokines attract stem cells from injury site, affecting recovery