Lec 69 Neuronal Injury Regeneration Repair

Question 1

Is there inflammation in necrosis? apoptosis?

Answer 1

no inflammation in apoptosis

yes inflammation in necrosis

Question 2

What is neurapraxia?

Answer 2

mild form of nerve damage; focal demyelination but axon itself not damaged

• -> decreased/slowed conduction through damaged part only
• -> heals completely in wks

Question 3

Does demyelination decrease conduction velocity or decrease AP amplitude?

Answer 3

decreases conduction velocity

Question 4

What is axonotmesis?

Answer 4

axon is disrupted/damaged but connecting tissue wrapping still intact

• -> part of axon distal to injury will degenerate [wallerian] and proximal part eventually regenerates
• -> heals in months

Question 5

What is neurotmesis?

Answer 5

connective tissue wrapping of nerve is damage

• -> difficulty regenerating axon
• -> may have regrowth to wrong place
• -> recovery poor

Question 6

Do axons regenerate easier in PNS or CNS?

Answer 6

easier in PNS

Question 7

What is mech of wallerian degeneration

Answer 7

• intra-axonal organelle breakdown
• schwann cells help axon breakdown and recruit more cells
• macrophages clean up debris
• path cleared for axons to grow proximal –> distal

= degeneration of injured axon distal to lesion in order to clear way for proximal part to regenerate

–> works well in PNS but not CNS

Question 8

What is role of schwann cells in regeneration?

Answer 8

secrete stimulatory factors that help regeneration = regeneration-association genes [RAGs]

Question 9

What are growth cones?

Answer 9

dynamic structures in PNS that grow using polymerization/depolymerization of actin/microtubules

Question 10

What happens in axonal repair in CNS?

Answer 10

• wallerian degeneration is inefficient –> myelin debris left behind + astrocytes lay down glial scarring
• OLGs and astrocytes secrete inhibitors to regeneration [myelin inhibitors, scar tissue]
• both CNS and aged neurons lack RAGs
• failed regeneration –> retraction bulbs = contain disorganized array of microtubules

Question 11

What are extrinsic inhibitors in CNS? what cells produce them?

Answer 11

• oligodendrocytes –> myelin associated inhibitors
• astrocytes –> chrondoitin sulfates
• astrocytes + fibroblasts –> fibrous scar tissue

Question 12

What is intrinsic growth potential in PNS vs CNS?

Answer 12

PNS = 1-3 mm/day
CNS = 0.1 mm/day

Question 13

What are extrinsic advantages of PNS regeneration?

Answer 13

• schwann cells secrete stim factors vs OLGs/astrocytes in CNS inhibit
• schwann start breakdown and recruit macrophages
• OLGs in CNS slower clearing dead axon tissue; astrocytes make fibrous glial scar that blocks growth

Question 14

What are intrinsic advantages of PNS?

Answer 14

• PNS neurons express growth-related genes/regeneration associated genes = have intrinsic growth potential
• in CNS = regeneration as slower pace if at all
• PNS neurons have receptors and signal transduction machinery –> allows them to grow in response to neurotrophins and retrograde injury signals

Question 15

What does failed regeneration look like?

Answer 15

try to regrow ad end in bulbs but stop = retraction bulbs

Question 16

What are good prognostic factors for outcome?

Answer 16

• reduced secondary damage via hypervigilant monitoring of vital signs, electrolytes, germs
• aggressive prolonged rehabilitation

Question 17

What is CNS plasticity?

Answer 17

rerouting not regenerating of neurons = regulating multiple facotrs in CNS to get around the injury

Question 18

What are short term mech of neural plasticity?

Answer 18

• synapse regulation = dendritic spine growth and pruning
• receptor regulation = trafficking of receptors toward synaptic cleft + recycling them back
• transmitter regulation
• network adaptation and plasticity

Question 19

What is synapse regulation?

Answer 19

mech of short term neural plasticity

- make synapse stronger or weaker in order to increase learning

Question 20

What is example of network adaptation?

Answer 20

task training in single hand causes selective increase in baseline excitability of that muscle group

Question 21

What are long term mechs of neural plasticity?

Answer 21

sprouting = rerouting of connections
pruning = consolidation of new circuits after period of regrowth [remove connections]

Question 22

How does learning skill help stimulation of cortical networks?

Answer 22

activity improves regeneration of netowkrs
learning variety of skilled, task-specific repetitive tasks = better than general exercise alone –> better stimulation cortical networks

repetitive tasks needed to maintain goals/consolidate circuits

Question 23

What are principles of rehabilitation?

Answer 23

promotes pruning of new connections

• learned skilled, relevant tasks better than general exercise
• -> skilled tasks stimulate cortical networks
• -> task specific real life skill more motivating and prune
• -> repetition maintains gains and consolidates circuits

Question 24

What is constraint-induced movement therapy?

Answer 24

constrain good limb in order to force pt to practice with injured limb = principle that hemispheres compete with each other via reciprocal inhibitory signals

physical restrain helps injured cortex promote plasticity

random practice order rather than ordered blocks

Question 25

Where are embryonic stem cells derived from?

Answer 25

blastocyst inner cell mass 4-5 days post fertilization

• usually from excess IVF-derived embryos NOT aborted fetuses
• source of pluripotent stem cells

Question 26

What are pluripotent stem cells?

Answer 26

can form endo/meso/ectoderm
cannot form trophoblast
immortal/renewable
no-autologous

Question 27

Where are fetal stem cells derived from?

Answer 27

fetal or extra-fetal tissue [amniotic fluid or umbilical cord blood]
does not necessarily disrupt fetal viability [but can come from aborted fetuses]
multipotent cells

Question 28

What are multipotent stem cells?

Answer 28

can differentiate into many but not all types

Question 29

Where are adult stem cells derived from?

Answer 29

mature tissues like bone marrow, skin, GI, adipose, cardiac, brain, dental pulp
oligopotent

Question 30

What are synonyms for adult stem cells?

Answer 30

mesenchyma stem cell

stromal stem cell

Question 31

What are oligopotent stem cells?

Answer 31

can differentiate into some cell types but basically lineage specific

ex. bone marrow stem cells –> all hematopoietic cell types

Question 32

What is somatic cell nuclear transfer?

Answer 32

adult somatic cell nuclei transferred into enucleated donor egg cells
adult nucleus reprogrammed by donor egg cytoplasm
pluripotent but not completely autologous

could use to clone animals

Question 33

What are induced pluripotent stem cells?

Answer 33

stem cell genes activated in adult somatic cells

have pluripotent stem cells that are 100% autologous

Question 34

What are uses of stem cells?

Answer 34

• developmental studies
• disease-specific cells for in vitro drug screening [to see which pt responds best to which drug]
• cell transplants
• organ transplants

Question 35

What are best targets for stem cells?

Answer 35

pathological processes that accept 1 type of neuron at 1 site