Nerve regeneration

Question 1

Describe the process of Wallerian degeneration and list the typical histological features that accompany it (3)

Answer 1

Degeneration of severed axons after injury. Proximal: chromatolysis, swelling of cell body. Distal: degradation/phagocytosis of disconnected axon and associated myelin sheath by macrophages and Schwann cells

Question 2

Outline the role of Schwann cells in the regeneration of peripheral nerves (4)

Answer 2

Remove debris, provide growth promoting substrate and guidance for regenerating axon, promote neuron survival by secreting neurotrophic factors, re-myelinate

Question 3

Describe the role of the three (3) major types of glia/supporting cells in the failure of axon regeneration in the CNS (6)

Answer 3

Oligodendrocytes: release/upregulation of neurite growth inhibitory proteins; astrocytes: glial scar formation & upregulation of axon growth inhibitory proteoglycans; microglia: may further damage & kill stressed neurons

Question 4

Outline the role of Schwann cells in the regeneration of peripheral nerves (3) [x3]

Answer 4

Remove debris, provide growth promoting substrate and guidance for regenerating axon, promote neuron survival by secreting neurotrophic factors, re-myelinate

Question 5

Describe the role of the three (3) major types of glia/supporting cells in the failure of axon regeneration in the CNS (4½)

Answer 5

Oligodendrocytes: Release/upregulation of neurite growth inhibitory proteins

Astrocytes: Glial scar formation and upregulation of axon growth inhibitory proteoglycans

Microglia: May further damage and kill stressed neurons

Question 6

Describe the process of Wallerian degeneration & list the typical histological features that accompany it (3)

Answer 6

Degeneration of severed axons after injury. Proximal: chromatolysis, swelling of cell body. Distal: degradation/phagocytosis of disconnected axon and associated myelin sheath by macrophages and Schwann cells

Question 7

State the cause of Wallerian degeneration and outline its typical microscopic features (3)

Answer 7

When nerves/axons are severed; chromatolysis, swelling of neuronal cell body, degradation of disconnected axon and associated myelin sheath

Question 8

Describe the process of Wallerian degeneration (2)

Answer 8

Chromatolysis, swelling of cell body, degradation of disconnected axon and associated myelin sheath

Question 9

When a lesion in the nervous system occurs & nerve connections are disrupted, the injured neurons show certain distinct histological features. List these features (2)

Answer 9

Chromatolysis, swelling of cell body, degradation of axon and myelin sheath

Question 10

Name the process (1)

Answer 10

Wallerian degeneration

Question 11

Describe the process of Wallerian degeneration (2)

Answer 11

Chromatolysis, swelling of cell body, degradation of disconnected axon and associated myelin sheath

Question 12

State the cause of Wallerian degeneration and outline its typical microscopic features (3)

Answer 12

When nerves/axons are severed; chromatolysis, swelling of neuronal cell body, degradation of disconnected axon and associated myelin sheath

Question 13

Describe the influence of glial cells on neurons attempting to regenerate axons after CNS injury (4) [x2]

Answer 13

Overall, they prevent axon regeneration. Oligodendrocytes: express neurite-growth inhibitory proteins, e.g. Nogo; astrocytes: turn reactive, form glial scar and express axon-growth inhibitory proteoglycans; microglia: remove debris but promote inflammatory reaction and may release cytotoxic factors damaging neurons

Question 14

Outline the role of the following cell types after an injury to the nervous system:

Schwann cells (2)

Answer 14

Phagocytosis of debris, expression of axon growth-promoting cell adhesion molecules, support of neuron survival and axon re-growth by neurotrophin secretion

Question 15

Oligodendrocytes (2)

Answer 15

Inhibition of axon regeneration through up-regulation of several growth inhibitory proteins

Question 16

Astrocytes (2)

Answer 16

Hypertrophy and formation of glial scar: mechanical barrier to axon re-growth, as well as up-regulation of inhibitory proteoglycans

Question 17

Microglia (2)

Answer 17

Phagocytosis of cell debris, degradation of extracellular matrix, but also promotion of inflammation and cytotoxic effects on neurones

Question 18

Contrast the recovery of a patient where the axon tracts in the spinal cord are completely severed, as opposed to a similar injury to a peripheral nerve.

In each case, is it likely that the lost functions can be restored? Justify your answer (10) (in your answer you should be able to List the different types of supportive cells in the PNS & CNS and outline the role that each plays after axonal injury)

Answer 18

Spinal cord: There is no recovery with a transaction of the spinal cord as CNS axons do not regenerate because astrocytes and oligodendrocytes express several proteins that inhibit axon regeneration after CNS injury, astrocytes form a glial scar that is an obstacle for regenerating axons, microglial cells clear away cell debris but may also kill injured neurones.

Peripheral nerve: there is a good chance of recovery of function because in the PNS, Schwann cells dedifferentiate and release neurotrophic factors that promote neurone survival. They also express cell adhesion molecules that promote axon regrowth. Eventually, they re-myelinate the regenerated axon.