6 – Regeneration and Plasticity

Question 1

Blood-CSF barrier:

Answer 1

-increased vascular network and projections of ependymal cells into ventricle=choroid plexus
>CSF production
-tight junctions between ependymal cells to protect CNS
*NO astrocytes here

Question 2

BBB:

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: CSF to brain
-waste removal: brain to CSF

Question 4

Lesion:

Answer 4

-any damage to any part of NS (PNS or CNS)
-various levels of severity=varying functional deficits

Question 5

What are some causes of lesions?

Answer 5

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

Question 6

How is information in the NS transmitted?

Answer 6

-via APs
>unidirectional within the axon and tracts/nerves
>soma to axon to terminal branches to post-synaptic cell
>afferent: towards CNS
>efferent: away from CNS

Question 7

Neuronal injury can consist of damage to the:

Answer 7

-cell body
-axon

Question 8

Damage to the axon:

Answer 8

-PNS = regeneration
-CNS = no regeneration
(limited)
*white matter

Question 9

Damage to the cell body:

Answer 9

-PNS = no regeneration
-CNS: = no regeneration
CELL DEATH =loss of synapse
*if damage to grey matter

Question 10

What happens if damage in peripheral area?

Answer 10

-axon is severed and divided into distal and proximal segment
>distal will die=not connected to cell body
>proximal: cell body is still intact=chance for regeneration

Question 11

Schwann cells:

Answer 11

-myelinating cells of PNS
-only myelinate ONE axon per Schwann cell

Question 12

Purpose of myelination:

Answer 12

-provide insulation and reorganization of cell membrane to accelerate AP conduction

Question 13

Oligodendrocytes and myelination:

Answer 13

-can myelinate multiple axons from different neurons

Question 14

Microglia:

Answer 14

-diverse roles
-embryological origins unclear
-balance of resting and active glia=critical for homeostasis

Question 15

Wallerian degeneration:

Answer 15

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

Question 16

Wallerian degeneration steps:

Answer 16

1. Axonal and myelin degeneration
2. Neuronal cell body response
3. Re-organization and re-growth

Question 17

Axonal and myelin degeneration: Schwann cells

Answer 17

-don’t generally die
-lose connections to damage axons

Question 18

Axonal and myelin degeneration: Schwann cells and macrophages

Answer 18

-phagocytize debris=results in demyelination
>occurs within WEEKS
*response from glia is rapid (Schwann cells)
-macrophages respond slower
*microglia play a LARGE role

Question 19

Why do macrophages respond slower (axonal and myelin degeneration)

Answer 19

-need recruitment via signalling factors
>released from injured axon/degenerating myelin/inflammation from injury

Question 20

Microglial play a LARGE role in Wallerian degeneration:

Answer 20

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

Question 21

After an injury, the neuron is NOT focused on:

Answer 21

-synthesizing NT or signal transmission
*main goal is to survive!

Question 22

Neuronal cell body response:

Answer 22

-Nissl substance is decreased
-changes in nucleus
>relaxing chromatin to allow for DNA replication

Question 23

Nerves in PNS organizations:

Answer 23

-fascicles with axon bundles
-endo-, peri- and epi- neurium
>*if connect together=can provide scaffold for new regenerating axons

Question 24

Re-organization and re-growth:

Answer 24

-degenerating axons and myelin leave a scaffold of endoneurium=pathway to guide regeneration
-Schwann cells line-up along the nerve pathway
>begin to secrete guidance molecules (nerve GF)
*damaged axon (proximal segment) sprouts and follows this pathway

Question 25

How long does it take for nerves in the PNS to be regenerated under IDEAL conditions?

Answer 25

-1-3mm/day (2cm/week)
>first axon reaches target in approximately 2 weeks
>staggered regenerative process over next 10+ weeks (slow)
*axons don’t always find correct target (endoneurium scaffold)

Question 26

What percent of axons, UNDER THE BEST CONDITIONS, regenerate in PNS:

Answer 26

-only 25-50% of axons can make appropriate connections following injury

Question 27

Axons don’t always find correct target (endoneurium scaffold):

Answer 27

-can produce incorrect or excessive neural connections in response to injury
-motor and sensory axons respond to same growth signals exhibited by Schwann cells

Question 28

Regeneration in CNS:

Answer 28

-typically does NOT occur
-distal segment degenerates=not connected to cell body
*’glial scar’ is formed

Question 29

In CNS, debris is VERY slowly cleared away (months) compared to PNS:

Answer 29

-oligodendrocytes either die (apoptosis) or go dormant -> poor myelin clearance
-since myelin clearance is not initiated, macrophages are NOT signalled (like in PNS) to aid in myelin clearance

Question 30

CNS ‘regeneration’ and oligodendrocytes:

Answer 30

-no Schwann cells
-do NOT secrete signalling growth factors
*=no axonal regeneration
>IF Schwan cells enter CNS, some regeneration is possible

Question 31

‘glial scar’ formed in CNS by:

Answer 31

-reactive astrocytes responding to cell injury and inflammation
>further inhibits regeneration and re-growth

Question 32

Recovery in PNS:

Answer 32

1. May sprout from an adjacent healthy axon to re-innervate the muscle fibers that have lost synapses
2. Muscles may hypertrophy to compensate for lost innervation and atrophy

Question 33

Recovery in CNS:

Answer 33

-always some recovery after injury, but is due to SYNAPTIC PLASTICITY rather than true regeneration