Regeneration and Plasticity Flashcards

1
Q

Blood-CSF barrier

A

-increased vascular network and projections of ependymal cells into the ventricle -choroid plexus
-where the CSF is produced
-there are tight junctions to protect CNS that are between the ependymal cells
*no astrocytes

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2
Q

Blood-brain barrier

A

-astrocytes induce endothelial cells of vessels to create tight junctions to protect CNS from blood borne pathogens

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3
Q

Brain-CSF barrier

A

-nutrients delivered from CSF to brain
-waste removed from brain to CSF

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4
Q

Lesion

A

-any damage to any part of the nervous system (PNS or CNS)
-various levels of severity with varying functional deficits

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5
Q

Causes of lesions

A

-trauma
-ischemia
-space occupying mass (neoplasia, foreign body)
-inflammation
-infection
-degenerative disorders
-congenital defects/structural abnormalities

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6
Q

Signal transmission

A

-information within the nervous system is transmitted via action potentials
*unidirectional within the axon and tracts/nerves (Soma to axon to terminal branches to post-synaptic cell)
-afferents (sensory) towards CNS, efferents away from CNS

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7
Q

Neuronal injury

A

-damage to the axon
-damage to the cell body

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8
Q

Damage to the axon

A

-PNS= regeneration
-CNS= no regeneration

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9
Q

Damage to the cell body

A

-no regeneration for either PNS or CNS
-will result in cell death and loss of synapse connection

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10
Q

Proximal vs. distal segments

A

-proximal segment closest to the CNS, distal segment closer to the tissue (muscle)
-if damage to segment occurs, then there is a chance for regeneration. But if cell body dies then no regeneration

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11
Q

Schwann cells

A

-myelinating cells of the PNS to provide insulation and reorganization of cell membranes to accelerate AP
-will only myelinated one axon per schwann cell

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12
Q

Oligodendrocytes

A

-myelinate cells in CNS to help with AP
-can myelinate multiple axons from different neurons

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13
Q

Microglia

A

-diverse roles in nervous system
-embryological origins are still unclear
-balance of resting and activated glia are critical for homeostasis

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14
Q

Wallerian Degeneration

A

-an active process of axonal degeneration (distal fragment) following injury in PNS or CNS

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15
Q

Steps of Wallerian Degeneration

A

1.axonal and myelin degeneration
2.neuronal cell body response
3.re-organization and re-growth

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16
Q

Axonal and myelin degeneration

A

Scwann cells generally don’t die but they do lose connections to the damaged axons

Schwann cells and macrophages phagocytose debris (such as myelin and neurofilaments) resulting in demyelination (takes a few weeks)
-the response from glia is rapid and the macrophages will respond slower (need recruitment via signalling factors that are released from the injured axon/degenerating myeline/inflammation from injury

Microglia play a large role in increased Wallerian degeneration

17
Q

Microglia’s role in Wallerian degeneration

A

-secrete factors to promote schwann cell proliferation
-phagocytosis of damaged cells
-secrete growth factors to promote axonal/nerve regeneration

18
Q

Neuronal cell body response

A

-after injury, the neuron is not focused on synthesizing neurotransmitters or signal transmission (which is typically its main goal)
-nissl substance is decreased
-changes in nucleus include relaxing chromatin to allow for DNA replication

19
Q

Re-organization and re-growth during Wallerian degeneration

A

-degenerating axons and myelin leave a scaffold of endoneurium, which can be used as the pathway to guide regeneration
-schwann cells line-up along the nerve pathway and begin to secrete guidance molecules (Nerve growth factor=NGF)
-damaged axons (proximal segment) sprouts and follows the pathway

20
Q

Regeneration time length in PNS

A

-nerves expected to regenerate 1-3 mm/day (2cm/week)
-first axon reaches target in approx. 2 weeks
-staggered regenerative process over the next 10+ weeks (slow)

21
Q

Unwanted sprouts

A

-regeneration can produce incorrect or excessive neural connections in response to injury. Motor and sensory axons respond to the same grow signals exhibited by schwann cell.
-can result in pain from connections forming at wrong spot resulting in unwanted feedback

22
Q

Regeneration in CNS

A

-typically does not occur
-distal segment degenerates as its no longer connected to the cell body

23
Q

Why does regeneration not really occur in CNS?

A

-debris is very slowly cleared away (months) compared to PNS (oligodendrocytes either die or become dormant which means they don’t clear away myelin, and no myelin clearance=no macrophages signalled to aid in myelin clearance)
-oligodendrocytes do not secrete signalling growth factors which means no axonal regeneration (BUT if some schwann cells enter CNS, then some regeneration is possible)
-glial scars form by reactive astrocytes responding to cell injury and inflammation (further inhibits regeneration and re-growth)

24
Q

Recovery vs. regeneration

A

-in PNS, regeneration is supported by growth factors released by schwann cells= functional regeneration occurs

-Recovery:
1. may sprout from an adjacent healthy axon to re-innervate the muscle fibers that have lost synapse
2. muscles may hypertrophy to compensate for lost innervation and atrophy

25
Q

Recovery in CNS

A

-there is always some recovery after injury
-occurs through synaptic plasticity rather than true regeneration