Lec 69 Neuronal Injury Regeneration Repair Flashcards
Is there inflammation in necrosis? apoptosis?
no inflammation in apoptosis
yes inflammation in necrosis
What is neurapraxia?
mild form of nerve damage; focal demyelination but axon itself not damaged
- -> decreased/slowed conduction through damaged part only
- -> heals completely in wks
Does demyelination decrease conduction velocity or decrease AP amplitude?
decreases conduction velocity
What is axonotmesis?
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
What is neurotmesis?
connective tissue wrapping of nerve is damage
- -> difficulty regenerating axon
- -> may have regrowth to wrong place
- -> recovery poor
Do axons regenerate easier in PNS or CNS?
easier in PNS
What is mech of wallerian degeneration
- 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
What is role of schwann cells in regeneration?
secrete stimulatory factors that help regeneration = regeneration-association genes [RAGs]
What are growth cones?
dynamic structures in PNS that grow using polymerization/depolymerization of actin/microtubules
What happens in axonal repair in CNS?
- 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
What are extrinsic inhibitors in CNS? what cells produce them?
- oligodendrocytes –> myelin associated inhibitors
- astrocytes –> chrondoitin sulfates
- astrocytes + fibroblasts –> fibrous scar tissue
What is intrinsic growth potential in PNS vs CNS?
PNS = 1-3 mm/day CNS = 0.1 mm/day
What are extrinsic advantages of PNS regeneration?
- 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
What are intrinsic advantages of PNS?
- 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
What does failed regeneration look like?
try to regrow ad end in bulbs but stop = retraction bulbs
What are good prognostic factors for outcome?
- reduced secondary damage via hypervigilant monitoring of vital signs, electrolytes, germs
- aggressive prolonged rehabilitation
What is CNS plasticity?
rerouting not regenerating of neurons = regulating multiple facotrs in CNS to get around the injury
What are short term mech of neural plasticity?
- synapse regulation = dendritic spine growth and pruning
- receptor regulation = trafficking of receptors toward synaptic cleft + recycling them back
- transmitter regulation
- network adaptation and plasticity
What is synapse regulation?
mech of short term neural plasticity
- make synapse stronger or weaker in order to increase learning
What is example of network adaptation?
task training in single hand causes selective increase in baseline excitability of that muscle group
What are long term mechs of neural plasticity?
sprouting = rerouting of connections pruning = consolidation of new circuits after period of regrowth [remove connections]
How does learning skill help stimulation of cortical networks?
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
What are principles of rehabilitation?
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
What is constraint-induced movement therapy?
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
Where are embryonic stem cells derived from?
blastocyst inner cell mass 4-5 days post fertilization
- usually from excess IVF-derived embryos NOT aborted fetuses
- source of pluripotent stem cells
What are pluripotent stem cells?
can form endo/meso/ectoderm
cannot form trophoblast
immortal/renewable
no-autologous
Where are fetal stem cells derived from?
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
What are multipotent stem cells?
can differentiate into many but not all types
Where are adult stem cells derived from?
mature tissues like bone marrow, skin, GI, adipose, cardiac, brain, dental pulp
oligopotent
What are synonyms for adult stem cells?
mesenchyma stem cell
stromal stem cell
What are oligopotent stem cells?
can differentiate into some cell types but basically lineage specific
ex. bone marrow stem cells –> all hematopoietic cell types
What is somatic cell nuclear transfer?
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
What are induced pluripotent stem cells?
stem cell genes activated in adult somatic cells
have pluripotent stem cells that are 100% autologous
What are uses of stem cells?
- developmental studies
- disease-specific cells for in vitro drug screening [to see which pt responds best to which drug]
- cell transplants
- organ transplants
What are best targets for stem cells?
pathological processes that accept 1 type of neuron at 1 site
