Neural Repair and Regeneration, Space

Question 1

3

Can the brain repair itself?

Answer 1

• Functional reorganization without large scale repair
• Requires behavior rehabilitation

Take home message – the adult brain is plastic and can bypass damaged areas. However, recovery is limited

Question 2

4

Describe problems with CNS regeneration

Answer 2

1. Neurons do not divide
2. Neurons have complicated structure and specific targets
3. Non-neural factors inhibit regrowth in the CNS
4. There is very little intrinsic regeneration in the CNS
5. PNS regeneration is robust

Question 3

5

Identify the 3 types of neural repair or regeneration

Answer 3

1. Axon regrowth in the PNS
2. Restoration of damaged central nerve cells
3. Wholesale genesis of new neurons

Question 4

6

What are the challenges of Axon regrowth?

Answer 4

• Axon guidance cues
• Synapse formation
• Synaptic refinement

Question 5

7

Do axons in the PNS regenerate?

Answer 5

Synapses and axons can regenerate. Gradually restored function.

distal and proximal regions of a nerve must be realigned and sutured for regeneration to happen
-must graft or use scaffold if not alligned

Axons degenerate distal to the injury
Macrophages clear debris
Exercise promotes nerve regeneration

• ECM
  
  • a specialized extracellular matrix that forms tubes around each axon. Axons grow within each tube.
  • ECM provides axon guidance cues
• Schwann cells in PNS promote/ guide axon regrowth
  
  • after macrophages clear debris the Schwann cells form Bands of Bungner
  • Specialize the ECM to provide the “tubes” for regrowth
  • secrete neurotrophic factors and guidance cues
  • Once the axon reaches its target, Schwann cells then myelinate the axons.

Question 6

15

CNS Axon Regrowth

How does CNS injury differ from PNS injury? Can CNS axons regrow?

Answer 6

Differences in Injury:
Vast cell death
    -Damage engages necrotic and apoptotic mechanisms of neighboring neurons.
Glial inhibition
Generates a non-permissive environment

CNS axons can regenerate in the right environment

Question 7

Do Dendrites regenerate?

Answer 7

Dendrites in Drosophila regenerate, havent yet studied in mammals

Dendritic regeneration uses different molecular pathways than axon regeneration

Question 8

18

Discuss injury and apoptosis in the CNS

Answer 8

1. injury causes large scale cell death
2. Apoptosis is induced by excitotoxicity (also apoptosis in neighboring cells) or inflammation (which also release cytokines to recruit immune cells)
3. Results in caspase-3 activation

POTENTIAL CAUSES:

• DNA damage
• Hypoxia
• stress
• growth factor withdrawal

RESULTS OF APOPTOSIS:

• chromosome condensation
• DNA fragmentation
• membrane blebbing
• cytoskeletal changes

Question 9

Do Dendrites regenerate?

Answer 9

Dendrites in Drosophila regenerate, havent yet studied in mammals

axon and dendrite generation utilize different molecular mechanisms of regeneration.

Question 10

20

Describe how Immunomodulation helps create permissive environment

Answer 10

Inflammatory response promotes axon regrowth in the CNS but Inflammation can also cause toxicity

Question 11

23

What are the challenges of wholesale genesis of new neurons?

Answer 11

• Axon guidance, cell polarity, trophic factors
• Availability of multipotent neural stem cells
• Location of neural stem cell and migration
• A permissive environment

Question 12

25

Discuss Neurogenesis

Answer 12

Non-mammals:
- Neurogenesis occurs in non-mammals

Mammals:

1. Evidence in mice, rats, and monkeys
   - Hippocampus and olfactory bulb
2. Generate interneurons and glia
3. Very few are incorporated

Stem cells originate from the subgranule zone or anterior subventricular zone

Neural stem cells migrate along the rostral migratory stream (RMS) in mammals

Question 13

Is there adult neurogenesis in humans?

Answer 13

only in the hippocampus

• Neural stem cells generate neurons and glia.

Question 14

17

What are the challenges of Restoration of injured CNS nerve cells

Answer 14

1. Reactivation of cell polarity mechanisms
2. New dendrites, axon, synapses all in the right places
3. Avoiding cell death
4. Must overcome glial inhibition

Question 15

Discuss Glia inhibition regeneration

Answer 15

1. Microglia: Immune cells of the CNS
2. Astrocytes: Release inhibitor Sema3A, slit, ephrins
3. Oligodendrocytes: Myelin components inhibit axon growth (MAG), and NogoA blocks axon growth

STARK contrast to PNS!

NOTE: Many different types of glia are recruited to the injury site. These cells provide many inhibitory cues and form a scar that provides physical inhibition of axon growth.

Question 16

22

Provide a summary of CNS Regeneration

Answer 16

1. Many CNS axons have the intrinsic ability to regenerate
2. Glia inhibit regeneration – non-permissive environment
3. Injuries cause broad cell death
4. Immunomodulation is one aspect of providing a permissive environment
5. Gene therapy can promotes intrinsic regeneration

Question 17

Name the 3 vestibular afferent innervation types

Answer 17

calyx, dimorphic, and bouton

Question 18

Summarize Space effects on vestibular system

Answer 18

1. Gravity level does not affect cell polarization
2. Development in microgravity produces vestibular changes
   
   • Afferent innervation of otolith receptors is affected by altered gravity environments. Macular innervation in 0g embryos consists of smaller diameter fibers. 2g embryo afferents have larger diameters.
3. Receptor hair cell number may be dependent upon gravity during development, but the effects are apparently weak and still under study.
4. Synaptogenesis in hair cells is affected by gravity.

Question 19

Why is space vestibular system important?

Answer 19

DNTM this slide, just read

In space, astronauts lose spatial orientation with no gravity vector to signal what is up. Rely on vision instead.

Vestibular neural processing:
- Establishes 3D spatial reference frame for neural computation of orientation, motion perception, dynamic behavioral coordination, muscle tone, and bone remodeling