CNS and PNS regeneration Flashcards

1
Q

what are the current treatments for spinal cord injury ?

A
  • spinal decompression
  • neuroprotection
  • rehabilitation
  • asssitive devices
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2
Q

what is the only certified treatment option for human patients with spinal cord injury?

A

rehabilitation

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3
Q

what is neuroprotection when it comes to treating spinal cord injury?

A
  • steroid treatments (inhibits swelling however, lots of side effects - in america a clinician can be sued if the patients is not provided steroids)
  • hypothermia (only in rare cases)
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4
Q

what are assited devices for spinal cord injury?

A

wheelchair, walker etc.

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5
Q

what and when would spinal decompression occur?

A

After trauma, damage to the spinal cord causes swelling. So, after an x-ray showing bone impeding on spinal cord itself (a surgeon would remove or stop this).

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6
Q

What animal can have full ‘CNS’ regeneration?

A

eel-like lamprey

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7
Q

If a lamprey experienced a lesion in its ‘spinal cord’ what would happen?

A

Tissue will grow a bridge across and within 11 weeks after injury the spinal cord will become fully functional

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8
Q

Why does axon regeneration fail in the CNS?

A

because of the inhibitory enviroment and the intrinsic lack of regenerative ability of the CNS

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9
Q

why can PNS axons regenerate?

A

because they have an intrinisically high regenerative ability and because of the permissive enviroment

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10
Q

describe successful Wallerian degeneration?

A
  • axonal injury occurs
  • macrophage clears the debris
  • no inhibitory molecules are present
  • and causes extended growth cone
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11
Q

why do crush lesions regenerate better than cut lesions in (PNS repair)?

A

due to the intact ECM as it acts as guidance channel for regrowth

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12
Q

what must be present in order for regeneration to occur in the PNS?

A

Schwann cells must be present and form bands of Büngner before acons growth can occur

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13
Q

what three things must happen and be present for PNS regeneration to occur?

A
  • the lesion gap must be vascularised
  • fibroblasts must form connective tissue
  • schwann cells must be present
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14
Q

what is a band of Büngner?

A

longitudinally aligned schwann cell strands that guide selectively regrowing axons

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15
Q

After PNS (crush) injury what are the regeneration rates like?

A

1-1.5 mm/ day

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16
Q

what does denervated mean?

A

a body part deprived of a nerve supply

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17
Q

how long do schwann cells in a denervared peripheral nerve remain permissive?

A

2-3 months

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18
Q

Due to the slow human peripheral nerver repair rate (1mm per day) what will it result in?

A
  • proximal structures will be well innervated (good nerve supply whereas distal structures will be poorly innervated
  • muscle endplates lose their ability to become re-innervated after around a year
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19
Q

what can happen to muscles in the absence of innervation?

A

severe atrophy

20
Q

What trial treatment uses the PNS enviroment to repair the CNS?

A

A PNS graft (medulla to spinal cord) can be transplanted to create a bridge for regrowing axons.
However, axons grew into the graft but not beyond (not back into the CNS).

21
Q

What did Abe and Cavalli discover?

A

that preconditioning lesions of the peripheral induce a robust regenerative response in the CNS

22
Q

What can crushing the peripheral nerve enhance?

A

CNS regeneration within the spinal cord of dorsal column axons
by:
- upregulating a series of genes (such as cAMP and GAP-43 and CAP-23)

23
Q

What growth-associated genes are upregulated when the peripheral nerve is crushed?

A

GAP-43 and CAP-23

24
Q

How can you mimic the effect of a crushed peripheral nerve?

A

injections of cAMP into the dorsal root ganglia

25
Q

Name the five key criteria for regeneration and repair success in the CNS?

A

1) neuron cell survival
2) axon elongation
3) axon guidance to target
4) appropriate target innervation and synapse formation
5) activation of target in functionally meaningful ay (functional repair)

26
Q

how does neuronal plasticity differ in developing NS vs adult/ mature NS?

A

Developing - high potential for plasticity
Adult - low plasticity and low regenerative ability

27
Q

what is the critical period in the nervous system?

A

the time during which reduction of neuronal numbers, remodeling of synapses and strengthening of connections occurs

28
Q

what is important about the critical period?

A
  • the most influential time during development since permanent connections are established
  • time when the system is most vunerable to external influences/ stimuli
29
Q

how can you test for ocular dominance plasticity?

A

ocular dominance stripes from unobscured eye can take over some of the obscured eyes territory (IF IN THE CRITICAL PERIOD)

30
Q

How does visual cortex differ in critical period vs mature/ adult?

A

critical period: mapping of visual cortex changes if one eye covered during development
adult: no change in mapping of the visual cortex if one eye covered in adult

31
Q

what are perineuronal nets?

A

composed of extracellular matrix (including CSPGs) which covers the cell soma and proximal dendrites of certain classes of neurons

32
Q

when are perineuronal nets formed?

A

end of the critical period

33
Q

how can perineuronal nets be shown ?

A

stained with WFA (wisteria floribunda agglutin)

34
Q

what is axotomy?

A

cutting or severing of a neurons axon

35
Q

describe what happens when axotomy and destruction of an axonal membrane occurs? (successful steps in growth cone formation )

A
  • entrance of calcium
  • causing activation of calcium voltage gated channels
  • more Ca2+ ions enter (from intracellular stores)
  • This activates calpains which digest the spectrin cortex
  • actin and MTs (microtubules) become depolymerised
  • the vacuole internalises
  • membrane begins to collapse at the cut end
36
Q

describe what happens when axotomy and destruction of an axonal membrane occurs up to the membrane collapse? (successful steps in growth cone formation )

A
  • entrance of calcium
  • causing activation of calcium voltage gated channels
  • more Ca2+ ions enter (from intracellular stores)
  • This activates calpains which digest the spectrin cortex
  • actin and MTs (microtubules) become depolymerised
  • the vacuole internalises
  • membrane begins to collapse at the cut end
37
Q

what happens in growth cone formation after growth cone formation?

A
  • the cut membrane reseals following membrane collapse by forming a sealing patch
  • Ca2+ levels are decreased to normal
  • actin and MTs are repolymerised
  • actin filaments assemble to generate force leading edge of lamellipodium
  • MTs polymerise and point their ends towards plasma membrane
38
Q

When axotomy occurs in the absence of calcium what happens?

A

regeneration fails and a static endbulb is formed

39
Q

where does the material needed to make a new growth cone come from?

A

1) recycling of axonal molecules (actin, tubulin)
2) transport vesicles on their way to the axon terminals
3) local translation of mRNAs
4) taken in from the enviroment

40
Q

when axotomy occurs what problems can growth cone regeneration (GCR) cause?

A

axotomy leads to upregulation of new proteins in cell bodies, which are needed for axon growth. GCR may happen too fast for these molecules to arrive however.

41
Q

Name three CNS myelin inhibitors?

A
  • Nogo-A
  • MAG
  • OMgp
42
Q

where are the three myelin inhibitors expressed and what do they do?

A

they are expressed on oligodendrocytes, where they inhibit axon regeneration.

43
Q

What does MAG do?

A
  • myelin-associated glycoprotein
  • localised to compact, mature myelin
  • stabilises neuronal networks
  • growth permissive to embryonic neurons
  • it is released upon damage into the lesion
44
Q

what does Nogo-A do?

A
  • acts through a receptor complex involving p75 and NgR
  • affecting axon gtowth via calcium and RhoA signalling
45
Q

what does OMgp do?

A
  • its a GPI-anchored protein
  • that is also expressed by neurons
  • mediates cell-cell interactions at nodes of ranvier
46
Q

What possible future treatments have surfaced to combat melin debris?

A
  • gold fish CNS has been researched as has shown myelin has sometimes not been inhibited