Neural regeneration

Question 1

What is the major difference between the CNS and the PNS in terms of regeneration?

Answer 1

PNS will regenerate, CNS will not

Question 2

When damage occurs to a peripheral nerve, which portion of the nerve can regenerate? In which direction?

Answer 2

Proximal portion of the axon can regenerate distally

Question 3

Is neuronal repair in the PNS full or partial?

Answer 3

Can be full, but is often partial

Question 4

If a peripheral nerve’s cell body is in the CNS, can it still undergo regeneration?

Answer 4

If the axon is damaged in the periphery, the proximal axon can regenerate distally

Question 5

What happens when neuronal injury occurs in the CNS?

Answer 5

Some neurons die

Some neurons retract processes but can sprout

Glial scars inhibit regrowth

Question 6

What determines the extent of neuronal repair in the CNS (ie. whether full or partial repair occurs)?

Answer 6

Severity of neuronal injury

Location of injury

Question 7

What are the three broad differences between the CNS and the PNS that allows the PNS to regenerate, but not the CNS?

Answer 7

NS structure

Cell types present

Molecules and guidance/repellent cues

Question 8

Describe the changes that occur in peripheral nerves after injury?

Answer 8

2 weeks post-injury: nucleus moves to the periphery, loss of Nissl substance, Wallerian degeneration, muscle fibre atrophy

3 weeks post injury: Schwann cells proliferate, nucleus moves centrally, growing axons penetrate Schwann cell cord, muscle fibre atrophy

3 months post injury: successful regeneration, muscle fibre regeneration

Question 9

What is Wallerian degeneration?

Answer 9

Degeneration of axon and myelin sheath below the site of injury

Question 10

What happens to a neuron if it does not regenerate successfully?

Answer 10

Neuroma formation

Question 11

Why might unsuccessful regeneration occur and result in neuroma formation?

Answer 11

Growing axon cannot find right target

Question 12

Is repair faster if the neuron is cut or crushed? Why?

Answer 12

Faster when crushed, because the Schwann cells and ECM (which act as a guide) remain continuous

More precise alignment allows better recovery and regeneration

Question 13

What is the main therapeutic approach to PNS injury?

Answer 13

Microsurgery to reattach proximal and distal stumps or a nerve graft

Question 14

Decsribe the primary injury that occurs in CNS neural injury?

Answer 14

PRIMARY INJURY

Immediate: Physical damage - cell loss

Question 15

Describe the secondary injuries that occur in CNS neural injury?

Answer 15

SECONDARY INJURY

Minutes to hours: ischaemia, Ca influx, lipid peroxidation and free radical production, glutamate excitotoxicity, BBB breakdown

Hours to days/weeks: immune cell infiltration, microglial activation, cytokines, chemokines, metalloproteases

Days/weeks: axonal degeneration, demyelination, apoptosis, astrocytic gliosis and glial scar, cavity formation

Question 16

What must be achieved in order to effectively repair the CNS?

Answer 16

Question 17

What broad features inhibit axonal regrowth?

Answer 17

Lack of trophic support

Injury environment inhibiting growth

Question 18

How can a lack of trophic support be combatted in order to support axonal regeneration?

Answer 18

Provide growth promoting factors eg. neurotrophins

Question 19

How can the injury environment be altered so that it does not inihibit axonal growth?

Answer 19

Inhibit growth blocking factors: astrocytic gliosis and glial scar, myelin inhibitors, developmental guidance molecules

Question 20

Describe the difference between axonal plasticity and axonal regeneration?

Answer 20

Plasticity: axons sprout; those near the injured neuron grow extra processes

Regeneration: neuron that was damaged grows a new axon

Question 21

Describe astrocytic gliosis?

Answer 21

Astrocytes become hypertrophic, proliferate, interdigitate processes, secrete cytokines and growth factors, secrete ECM, upregulate axon guidance molecules

This all leads to glial scar formation

Question 22

Why can astrocytic gliosis be inhibitory to neuronal regeneration?

Answer 22

Glial scar forms a barrier between undamaged tissue and and injury site

Question 23

Which techniques targetting astrocytic gliosis have resulted in increased neuronal regeneration?

Answer 23

Blocking of astrocyte ECM

GFAP/Vimentin double knockout

Astrocyte ablation

Question 24

Which molecules in the injury environment inhibit axon regrowth?

Answer 24

Myelin inhibitors on myelin debris

Guidance molecules on actiavted astrocytes

Question 25

Which particular myelin proteins are inhibitory in the injury environment, and why are they inhibitory?

Answer 25

Nogo, MAG and OMgp

All bind to Nogo receptor, which activates the Rho signalling pathway > inhibits axon growth

Question 26

How are myelin proteins being targetted to encourage axonal regrowth?

Answer 26

Gene knockouts, Nogo blockers (Anti-Nogo antibody) and Rho inhibitors

Question 27

What are axon guidance molecules?

Answer 27

Molecules that promote, repel or guide growing axons

Question 28

Describe why Rho activation inhibits axonal growth?

Answer 28

Causes growth cone to shrink

Activates astrocytes

Question 29

Compare and contrast the CNS and PNS injury environments?

Answer 29

Question 30

Describe two strategies for using stem cells to repair the nervous system?

Answer 30

1. Transplant stem cells/neurons
2. Use drugs to activate stem cells already present in NS

Question 31

What are the two main neurogenic regions in the brain?

Answer 31

Subventricular zone

Subgranular zone

Question 32

Why don’t endogenous neural stem cells nromally effectively repair the CNS?

Answer 32

Cells must proliferate, migrate, differentiate, and then survive

Question 33

What is the most important non-pharmacological form of therapy for functional regeneration?

Answer 33

Physical therapy and muscle/neuronal activity