Neural Regeneration

Question 1

what is the main environmental difference between CNS and PNS neuron regeneration?

Answer 1

the glial environment

Question 2

can CNS neurons sprout and make new connections like PNS neurons?

Answer 2

Yes, but glial environment inhibits it

Question 3

What is the structural difference between CNS and PNS neurons?

Answer 3

there is connective tissue around PNS neurons to help regrowth

PNS neurons have 1 to 1 relationship. CNS is one to many

Question 4

2 weeks post-injury, what will happen to a PNS neuron

Answer 4

cell soma changes morphology, such that nucleus moves to periphery

loss of Nissl substance, and ribosomes stop working, forming chromolysis

axon breakdown

muscle fibre atrophy

Question 5

What is Wallerian Degeneration

Answer 5

degeneration of myelin on axon distal to site of injury

debris is cleaned up by macrophages

Question 6

what happens 3-weeks post PNS injury

Answer 6

Schwann cells proliferation forming a compact cord, guiding axon regrowth

nucleus moves central again

Question 7

What happens if the regeneration is successful

Answer 7

electrical activity will restore and muscle fibre regenerate

Question 8

What happens if the regeneration is unsuccessful

Answer 8

neuroma formation, and patient gets unwanted sensation and pain from the bundle of nerve sprouts

Question 9

Does neuron regenerate faster in a crushed injury? Why?

Answer 9

Yes, faster than having it cut, because the route of connective tissue is still intact. Neurons regenerate better with better alignment

Question 10

T/F Oligodendrocytes encourage neural growth

Answer 10

False, oligodendrocytes are very inhibitory to regrowth

Question 11

What is the treatment to primary CNS neural injury

Answer 11

remove primary causative agent to minimise extent of damage

Question 12

What is an agent used to minimise CNS damage

Answer 12

tissue plasminogen activator (tPA) used in stroke

Question 13

What are some immediate secondary damage to CNS neurons

Answer 13

degenerative chemical insults in much larger area, including
ischaemia,
Ca influx,
free radical production,
glutamate excitotoxicity (glutamate released but not cleared)
BBB breakdown allow other things to enter

Question 14

What are some secondary damage that develop in hours to days

Answer 14

immune cell infiltration
microglial activation
inflammatory mediators

Question 15

What are some secondary damage that develop in days to weeks

Answer 15

axonal degeneration in large area
demyelination 
slow phagocytosis encouraging apoptosis 
glial scar formation
meningeal fibroblast migration (scar)

Question 16

what are the four potential ways of repairing CNS

Answer 16

protect surviving cells
axonal regeneration with functional integration
modulate astrocytic gliosis
neuron stem cells

Question 17

Why won’t axons regrow in CNS

Answer 17

lack of trophic factor to guide growth

environment inhibits regrowth

Question 18

What is trophic support treatment? Why has it stopped

Answer 18

provide growth factors like NGF and BDNF to encourage axonal growth, but it causes neuropathic pain

Question 19

what is axonal plasticity? How can it be enhanced?

Answer 19

damaged axon retracts, and nearby axon sprouts an extra process to re-innervate

can be enhanced by exercise

Question 20

What is the cytoskeletal protein of astrocyte that inhibits axonal regrowth? What is its normal role

Answer 20

glial fibrillary acidic protein (GFAP)

helps with neuronal stability

Question 21

Why can’t we just ablate the astrocytes to prevent glial formation

Answer 21

astrocytes are very important for wound repair. A lack of astrocyte will cause increased inflammation, increased tissue destruction, and BBB repair inhibition

Question 22

what are the three myelin inhibitor? What do they bind to?

Answer 22

Nogo
Myelin associated glycoprotein
OMgp

all bind to Nogo receptor, resulting in Rho pathway and growth inhibition

Question 23

What are the two ways of utilising stem cells

Answer 23

mobilise endogenous cells

transplant exogenous cells

Question 24

where are the endogenous stem cells found

Answer 24

subventricular zone of the lateral ventricle

subgranular zone of the dentate gyrus in hippocampus

Question 25

where do the cells of subventricular zone go to?

Answer 25

migrate to the olfactory bulb

Question 26

How can we promote axonal regrowth

Answer 26

by blocking inhibitory molecules and promote axon guidance molecules like Eph