Neuronal disorder and repair

Question 1

What is Wallerian degeneration?

Answer 1

Active process of degeneration that results when a nerve fibre damaged and the part of the axon distal to the injury degenerates.

Question 2

What do oligodendrocytes required to survive?

Answer 2

Oligodendrocytes require axon signals to survive.

Question 3

What happens to oligodendrocytes in injury?

Answer 3

Upon injury, the oligodendrocytes fail to clean up the myelin sheaths and their debris - glial scar formation -inhibits regeneration and reinnervation.

Question 4

What is Vincristine peripheral neuropathy?

Answer 4

Vincristine = chemotherapy medication required to treat a number of types of cancer.

Vincristine works by binding to the tubular protein, stopping tubular dimers from polymerising to form microtubules. In cancer treatment stops chromosome separation and leads to apoptosis.

Symptoms of neuropathy are mainly sensory - pain, tingling and numbness. Sometimes motor nerves and ANS involvement. Thought that microtubule disturbance in nerves = cause.

Question 5

What is neuropraxia?

Answer 5

Transient block (no degeneration and minimal lesion) recovers completely and rapidly

Question 6

What is axonotmesis

Answer 6

Damage causes degeneration, but the nerve supporting structure remains

Question 7

What is neurotmesis

Answer 7

Complete anatomical division of the nerve

Question 8

Can the PNS regenerate?

Answer 8

Yes,

Schwann cells dedifferentiate and upregulate production of both neurotrophic factors and growth promoting ECM.

Question 9

What happens when there is CNS damage?

Answer 9

Mechanical injury to the adult mammalian CNS always results in the formation of a lesion scar: a regeneration barrier.

Question 10

What happens to the BBB in CNS damage?

Answer 10

BBB breakdown

Question 11

What is the inflammatory response in response to CNS damage?

Answer 11

Recruitment of neutrophils
Recruitment of microglia cells/ macrophages, surrounding tissue accumulates with neutrophils, microglia, increased cytokines, induced inflammatory response and induced degeneration.

Question 12

What factors stimulate glial scar formation?

Answer 12

Inflammatory factors .

Question 13

What constitutes the glial scar?

Answer 13

Astrocytes, microglia and oligodendrocyte progenitor cells

mainly astrocytes

Question 14

What is a fibrotic scar consistent of? How?

Answer 14

Fibrotic scar formed by fibroblasts, which have invaded the lesion site from adjacent meningeal and perivascular cells.

Question 15

What is a theory about the impact of glial scars on healing?

Answer 15

Failure to regenerate is due to the blocking effect of the scar formed at the lesion site.

Question 16

What do reactive astrocytes and fibroblasts form at the scar interface? What is its role?

Answer 16

Glia limitans - protective in reconstituting the BBB, preventing neuronal degeneration and limiting the spread of damage

Question 17

What two ways do scars inhibit regeneration?

Answer 17

Physically and chemically

Question 18

How do scars inhibit regeneration chemically?

Answer 18

Inhibiting factors upregulated prevent regrowth (Chondroitin sulfate proteoglycan (CSPG) family, tenascin, semaphorin 3A, myelin-associated molecules and subtypes of the Eph receptors and their ligands ephrins)

Question 19

How do scars inhibit regeneration physically?

Answer 19

Transected axons stop at the border of the fibrotic scar due to its complex, densely packed structure

Question 20

What are neurotrophic factors?

Answer 20

Neurotrophic factors promote survival and growth of neurons.

Question 21

What effects do neurotrophic factors have?

Answer 21

autocrine and paracrine - promote neuron growth and glial growth

Question 22

How does neuronal cell death occur in CNS damage? (two ways)

Answer 22

Either from neurotoxicity - excess glutamate causes Ca2+ influx and cell death.

Or axotomy prevents neurotrophic retrograde transport so neutrons die.

Question 23

What cells make neurotrophic factors?

Answer 23

Schwann cells

Question 24

Cell therapy: possible application in Parkinson’s?

Answer 24

Can we exploit regeneration promoting PNS Schwann cells to repair CNS.

Use enzymes to remove the inhibitory side chains of CSPGs?

Inject neurotrophic factors.

Is neural transplantation an option?