Neural Regeneration

Question 1

Which nerves have better regeneration - ones in the PNS or ones in the CNS?

Answer 1

the PNS

Question 2

What happens to a peripheral nerve for the 2 weeks after nerve injury?

Answer 2

nucleus become peripheral, chromolysis, wallerian degeneration and muscle fibre atrophy

Question 3

What is wallerian degeneration?

Answer 3

degeneration of axon and myelin sheath below the site of injury - debris is phagocytosed by macrophages

Question 4

What happens to a peripheral nerve 3 weeks after nerve injury?

Answer 4

regeneration starts - the nucleus become more central, there are more nissl bodies, schwann cells proliferate and fill the nerve fibre and the growing axon penetrates the schwann cells

Question 5

How long does it take for the peripheral nerve to fully regenerate and restore electrical activity?

Answer 5

up to 3 months

Question 6

What is a neuroma?

Answer 6

a neuroma is the product of unsuccessful regeneration - a bundle of nerve fibres that can be painful

Question 7

Why is repair faster if a nerve is crushed rather than cut?

Answer 7

because the alignment of the nerve is a key factor - the better the alignment the better the outcome

Question 8

What is primary damage in the CNS?

Answer 8

the immediate physical damage and cell loss in a small site

Question 9

What is secondary damage in the CNS?

Answer 9

the degenerative insult around the area of primary damage due to ischaemia, calcium influx, lipid peroxidation and free radical production, glutamate excitotoxicity and blood brain barrier breakdown - followed by immune cell infiltration and activation - all of this will result in axon degeneration and demyelination

Question 10

What are the two factors which stop axonal regeneration in the CNS?

Answer 10

a lack of trophic support and inhibition by the injury environment

Question 11

What factors in the injury environment inhibit axonal regeneration in the CNS?

Answer 11

astrocytic gliosis and myelin (oligodendrocytes)

Question 12

What treatment has been trialed to counteract the lack of trophic support and why was it unsuccessful?

Answer 12

giving neurotrophins such as NGF and BDNF but has adverse effects such as neuropathic pain

Question 13

Why is astrocytic gliosis inhibitory to axonal regeneration?

Answer 13

because it provide a physical barrier to growth, it secretes an extracellular matrix that is inhibitory to growth and produces cytokines that are inhibitory to growth

Question 14

What treatment has been trialed to counteract the astrocytic gliosis?

Answer 14

blocking the molecule that activates astrocytes (TGFbeta) - didn’t work because it was activated by other molecules, blocking the activity of the extracellular matrix secreted by the astrocytes - had some efficacy, blocking the GFAP cytoskeleton molecule in astrocytes - had some efficacy, completely blocking astrocytes - detrimental

Question 15

What proteins produced by oligodendrocytes are inhibitory to axonal regeneration?

Answer 15

Nogo, MAG and OMgp

Question 16

What receptor do the inhibitory proteins produced by oligodendrocytes bind to and what pathway does this activate?

Answer 16

they all bind to the Nogo receptor which activates the rho A kinase pathway

Question 17

What treatments have been trialed to counteract the inhibitory proteins produced by oligodendrocytes?

Answer 17

Nogo blockers, rho inhibitors, anti-nogo antibodies

Question 18

What are axon guidance molecules?

Answer 18

molecules that promote, repel or guide growing axons in development that may be upregulated or re-expressed in the adult after injury e.g. EphA4

Question 19

Why is rho kinase potentially a good target for neural regeneration?

Answer 19

because it is a common pathway to target lots of inhibitory effects such as myelin inhibitors, axon guidance molecules, astrocyte activation

Question 20

What are the two potential ways to use stem cells to repair nervous system injuries?

Answer 20

transplant stem cells or activate cells already present

Question 21

What are the two main neurogenic regions in the adult mammalian brain?

Answer 21

the sub ventricular zone of the lateral ventricle and the sub granular zone of the dentate gyrus in the hippocampus