Regeneration Flashcards

1
Q

How can the visual system can be used as a model to demonstrate that CNS neurons fail to regenerate?

A

Severed RGCs in the optic nerve (dyed) cannot regenerate.

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2
Q

How can the rodent spinal cord can be used as a model to demonstrate that CNS neurons fail to regenerate?

A

If sectioning the corticospinal tract at the dorsal spinal cord hemisection and then injecting a retrograde tracer in the spinal cord, the CST below the lesion site will not be dyed.

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3
Q

A lesion of CNS axons creates a nasty environment that impedes regrowth. What exactly is impeding regrowth?

A

Immune cells, glial scar and myelin debris.

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4
Q

True or false: PNS neurons can regrow to some extent in mammals.

A

True.

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5
Q

Why was the grafting experiment of Aguayo paradigm-shifting?

A

Aguayo’s experiment demonstrated that when grafting PNS tissue into an injury site of the CNS, CNS neurons can regrow on the PNS tissue. This is ground-breaking because it shows that CNS neurons also have the intrinsic property to regrow, and that it is their environment that prevents them from doing so.

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6
Q

Are molecules inhibiting axonal regrowth in the CNS specific to myelin?

A

No, CNS neurons also generate inhibitory signals.

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7
Q

Nogo, the inhibitory signal for axonal regrowth in the CNS, comes from what cell? What happens to regrowth when KO?

A

Oligodendrocytes (CNS myelin). Regrowth is facilitated when Nogo is knocked-out.

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8
Q

Why is the BBB locomotor rating scale particularly useful?

A

Allows to determine level of regrowth only by observation (regain of function).

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9
Q

Name the major inhibitory component of SCI scar.

A

Astrocyte forming astrocytic scar penumbra (CSPGs).

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10
Q

What is the advantage of targeting an intracellular component of inhibitory molecules of axonal regrowth?

A

Inhibitory molecules are numerous and rely on multiple receptors. However, they most probably share downstream mechanisms. Therefore, targeting the latter allows to regulate the activity of an extensive number of inhibitory signals at the same time.

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11
Q

What happens to regrowth abilities of CNS neurons when inhibiting the Rho pathway? What model system can be used test this?

A

Blockade of the Rho pathway overcomes myelin- and CSPG-dependent neurite outgrowth inhibition = much more versatile regrowth abilities. The RGC pathway can be used (indeed works).

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12
Q

What is a way of improving regrowth capabilities without directly modifying neuron’s intracellular activity?

A

Bioactive scaffolds (providing favourable conditions for regrowth).

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13
Q

What is PTEN? What does modifying PTEN activity tell us about axon regeneration?

A

PTEN is a tumor growth inhibitor. KO PTEN allows very important regeneration. The same finding applies to SOCS3. This shows that intrinsic pathways exist for regulating axon regeneration.

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14
Q

True or false: immune factors always impede axonal regeneration.

A

False: some inflammatory factors such as oncomodulin can even promote regeneration.

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15
Q

How can regrowth of axons be spatially directed?

A

Injection of neurotrophic factors (rough).

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16
Q

How could cell replacement help to re-establish connections?

A

Use of STEM cells to create axonal bridges on which could fasciculate truncated neurons (that’s only one possibility).

17
Q

What is the advantage of using Induced Pluripotent Stem Cells (iPSCs) to treatment SCI?

A

Since they can originate from the patient, risks of graft rejection are much lower.

18
Q

What alternative method using STEM cells could be done for neuronal regrowth?

A

Reprogrammation of cells already at the site of damage (e.g., NG2 glia -> neuron).

19
Q

SUMMARY CARD:

List techniques that can be used to promote CNS regeneration.

A

List techniques that can be used to promote CNS regeneration:

-Silencing inhibitors by KO either ligand or receptor (e.g., Nogo)
-Silencing inhibitors by deactivating intracellular components (e.g., RhoA)
-Bioactive scaffolds
-Regulate intrinsic pathways that mediate axon regeneration (e.g., PTEN and SCOS3)
-Use of certain immune interactions (e.g., oncomodulin)
-Cell replacement strategies