Lecture 30-32: Injury & Repair of Nervous System

Question 1

Wallerian degeneration

Answer 1

Degeneration of axon and myelin sheath below site of injury
Debris phagocytosed by macrophages
Muscle fibre atrophy

Question 2

Unsuccessful regeneration in the PNS often leads to the formation of a

Answer 2

neuroma

Question 3

How do Schwann cells create a molecular environment that supports axon guidance and growth?

Answer 3

Schwann cells:

• Secrete extracellular matrix molecules such as laminin, fibronectins and collagen to provide structural support.
• Increase expression of cell surface molecules such as L1, N-CAM, N-cadherin, which bind to receptors on regenerating axons
• Near the site of injury increase expression of neurotrophic factors such as Brain-derived neurotrophic factor (BDNF)

Question 4

Growth cones express growth promoting proteins such as:

Answer 4

GAP-43, and integrins which bind to ECM molecules secreted by Schwann cells

Question 5

True or false:

When skeletal muscle fibres are denervated, the neuromuscular synaptic site degenerates after a few days.

Answer 5

False, the neuromuscular synaptic sites remain intact for weeks.

Question 6

Causes of inhibitory environment in the CNS:

Answer 6

Inhibitory molecules in myelin debris - Nogo, MAG

Astrocytic gliosis and the glial scar

Upregulation of developmental axon guidance molecules - semaphorins, Tenascin, CAMs, Eph/ephrin family

Question 7

Treatment for lack of trophic support

Answer 7

Encourage axons to regrow by providing growth-promoting factors such as neurotrophins e.g. NGF, BDNF

Question 8

Possible treatment for inhibition of axon regrowth by the injury environment

Answer 8

Blocking inhibitory factors such as myelin inhibitors and developmental guidance molecules

Question 9

Pros and cons of astrocytic gliosis

Answer 9

Pros:
   - Wound sealing
   - BBB repair
   - Secrete growth factors - NGF/BDNF
   - Increased glutamate transporters
Cons:
   - Physical barrier
   - Molecular barrier
   - ECM - CSPG, collagen IV
   - Secrete pro-inflammatory cytokines - TNFα, IL-1

Question 10

Main neurogenic regions in the adult mammalian brain

Answer 10

Subventricular zone (SVZ) of the lateral ventricle
Subgranular zone (SGZ) of the dentate gyrus in the hippocampus

Question 11

Major factors secreted by Schwann cells and muscle fibres during reinnervation of muscle

Answer 11

NGF and BDNF

Question 12

Mechanism of astrocytic gliosis

Answer 12

Upregulation of astrocyte cytoskeletal proteins such as GFAP which secrete inhibitory molecules such as chondroitin in its extracellular matrix and upregulate expression of developmental axon guidance molecules that inhibit growth after injury

Question 13

Factors that influence regenerative capacity in peripheral nerves

Answer 13

Macrophages RAPIDLY remove myelin debris
Schwann cells support intact axons and form peripheral myelin as well as secreting molecules required for successful regeneration

Question 14

Major developmental axon guidance molecules include

Answer 14

Eph/ephrins, semaphorins

Question 15

Myelin inbhibitors

Answer 15

Nogo
MAG
OMgp
All of these result in the activation of the Rho signalling pathway which inhibits axon growth

Question 16

Why don’t endogenous stem cells normally effectively repair the nervous system?

Answer 16

Most stem cell die within weeks.
As well as differentiating into neurones, neural stem cells differentiate into glia and oligodendrocytes
Expression of growth factors and inflammatory molecules post-injury changes migration course.