CNS and PNS regeneration Flashcards
what are the current treatments for spinal cord injury ?
- spinal decompression
- neuroprotection
- rehabilitation
- asssitive devices
what is the only certified treatment option for human patients with spinal cord injury?
rehabilitation
what is neuroprotection when it comes to treating spinal cord injury?
- 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)
what are assited devices for spinal cord injury?
wheelchair, walker etc.
what and when would spinal decompression occur?
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).
What animal can have full ‘CNS’ regeneration?
eel-like lamprey
If a lamprey experienced a lesion in its ‘spinal cord’ what would happen?
Tissue will grow a bridge across and within 11 weeks after injury the spinal cord will become fully functional
Why does axon regeneration fail in the CNS?
because of the inhibitory enviroment and the intrinsic lack of regenerative ability of the CNS
why can PNS axons regenerate?
because they have an intrinisically high regenerative ability and because of the permissive enviroment
describe successful Wallerian degeneration?
- axonal injury occurs
- macrophage clears the debris
- no inhibitory molecules are present
- and causes extended growth cone
why do crush lesions regenerate better than cut lesions in (PNS repair)?
due to the intact ECM as it acts as guidance channel for regrowth
what must be present in order for regeneration to occur in the PNS?
Schwann cells must be present and form bands of Büngner before acons growth can occur
what three things must happen and be present for PNS regeneration to occur?
- the lesion gap must be vascularised
- fibroblasts must form connective tissue
- schwann cells must be present
what is a band of Büngner?
longitudinally aligned schwann cell strands that guide selectively regrowing axons
After PNS (crush) injury what are the regeneration rates like?
1-1.5 mm/ day
what does denervated mean?
a body part deprived of a nerve supply
how long do schwann cells in a denervared peripheral nerve remain permissive?
2-3 months
Due to the slow human peripheral nerver repair rate (1mm per day) what will it result in?
- 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
what can happen to muscles in the absence of innervation?
severe atrophy
What trial treatment uses the PNS enviroment to repair the CNS?
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).
What did Abe and Cavalli discover?
that preconditioning lesions of the peripheral induce a robust regenerative response in the CNS
What can crushing the peripheral nerve enhance?
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)
What growth-associated genes are upregulated when the peripheral nerve is crushed?
GAP-43 and CAP-23
How can you mimic the effect of a crushed peripheral nerve?
injections of cAMP into the dorsal root ganglia
Name the five key criteria for regeneration and repair success in the CNS?
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)
how does neuronal plasticity differ in developing NS vs adult/ mature NS?
Developing - high potential for plasticity
Adult - low plasticity and low regenerative ability
what is the critical period in the nervous system?
the time during which reduction of neuronal numbers, remodeling of synapses and strengthening of connections occurs
what is important about the critical period?
- the most influential time during development since permanent connections are established
- time when the system is most vunerable to external influences/ stimuli
how can you test for ocular dominance plasticity?
ocular dominance stripes from unobscured eye can take over some of the obscured eyes territory (IF IN THE CRITICAL PERIOD)
How does visual cortex differ in critical period vs mature/ adult?
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
what are perineuronal nets?
composed of extracellular matrix (including CSPGs) which covers the cell soma and proximal dendrites of certain classes of neurons
when are perineuronal nets formed?
end of the critical period
how can perineuronal nets be shown ?
stained with WFA (wisteria floribunda agglutin)
what is axotomy?
cutting or severing of a neurons axon
describe what happens when axotomy and destruction of an axonal membrane occurs? (successful steps in growth cone formation )
- 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
describe what happens when axotomy and destruction of an axonal membrane occurs up to the membrane collapse? (successful steps in growth cone formation )
- 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
what happens in growth cone formation after growth cone formation?
- 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
When axotomy occurs in the absence of calcium what happens?
regeneration fails and a static endbulb is formed
where does the material needed to make a new growth cone come from?
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
when axotomy occurs what problems can growth cone regeneration (GCR) cause?
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.
Name three CNS myelin inhibitors?
- Nogo-A
- MAG
- OMgp
where are the three myelin inhibitors expressed and what do they do?
they are expressed on oligodendrocytes, where they inhibit axon regeneration.
What does MAG do?
- myelin-associated glycoprotein
- localised to compact, mature myelin
- stabilises neuronal networks
- growth permissive to embryonic neurons
- it is released upon damage into the lesion
what does Nogo-A do?
- acts through a receptor complex involving p75 and NgR
- affecting axon gtowth via calcium and RhoA signalling
what does OMgp do?
- its a GPI-anchored protein
- that is also expressed by neurons
- mediates cell-cell interactions at nodes of ranvier
What possible future treatments have surfaced to combat melin debris?
- gold fish CNS has been researched as has shown myelin has sometimes not been inhibited
