Regeneration and Plasticity

Question 1

Blood-CSF barrier

Answer 1

-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

Question 2

Blood-brain barrier

Answer 2

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

Question 3

Brain-CSF barrier

Answer 3

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

Question 4

Lesion

Answer 4

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

Question 5

Causes of lesions

Answer 5

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

Question 6

Signal transmission

Answer 6

-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

Question 7

Neuronal injury

Answer 7

-damage to the axon
-damage to the cell body

Question 8

Damage to the axon

Answer 8

-PNS= regeneration
-CNS= no regeneration

Question 9

Damage to the cell body

Answer 9

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

Question 10

Proximal vs. distal segments

Answer 10

-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

Question 11

Schwann cells

Answer 11

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

Question 12

Oligodendrocytes

Answer 12

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

Question 13

Microglia

Answer 13

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

Question 14

Wallerian Degeneration

Answer 14

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

Question 15

Steps of Wallerian Degeneration

Answer 15

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

Question 16

Axonal and myelin degeneration

Answer 16

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

Question 17

Microglia’s role in Wallerian degeneration

Answer 17

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

Question 18

Neuronal cell body response

Answer 18

-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

Question 19

Re-organization and re-growth during Wallerian degeneration

Answer 19

-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

Question 20

Regeneration time length in PNS

Answer 20

-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)

Question 21

Unwanted sprouts

Answer 21

-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

Question 22

Regeneration in CNS

Answer 22

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

Question 23

Why does regeneration not really occur in CNS?

Answer 23

-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)

Question 24

Recovery vs. regeneration

Answer 24

-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

Question 25

Recovery in CNS

Answer 25

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