Flashcards in Regeneration-VonB Deck (43):
What happens after you get axonal injury in the PNS?
Chromatolysis (cell body response)
What is Wallerian degeneration?
this is degeneration of the distal stump of a lesioned axon
this is done so that the growth cone has a good substrate
it isn't a passive process caused by lack of nutrients.
allows for invasion of macrophages & schwann cells
doesn't mess with intact axon fibers
What stains in a Nissl stain? Why is this such a good way of visualizing a neuron?
the rough ER stains in a Nissl Stain
**good way to visualize b/c neurons need a lot of proteins & thus have a lot of Rough ER
What shows up in a Nissl stain pic before & after an axonal lesion?
Before: Lots of purple for Rough ER
**centrally located nucleus
After: Grey, much less rough ER
**nucleus in a different position
What happens 2 weeks after an axonal lesion in the PNS?
Wallerian degeneration happens at the distal stump & you start to get a growth cone forming & bridging the gap
Also myelin & other tissue needs to be removed-done by Schwann & macrophage cells.
What happens 3 months after an axonal lesion in the PNS?
at this time you get functional reinnervation of your myofiber
What happens if you never get functional reinnervation of your myofiber?
then you get atrophy
if there is too much scar tissue-a growth cone can't get across
Aside from phagocytosis of myelin of messed up axonal fibers...what else do Schwann cells do after an axonal cut?
they secrete trophic factors
divide & form bands of bungner-->makes a tract for the growth cone
What does successful regeneration of PNS axon that has been cut require?
survival of cell body
functional connection with target
Which is more helpful for axonal regeneration? Schwann cells; Oligodendrocytes.
Definitely Schwann cells.
Oligodendrocytes aren't helpful-hurt the process of axonal regeneration in the CNS
If the distal & proximal stump of a severed nerve are far apart...what medical intervention might be necessary?
a nerve graft
the nerve won't become functional, but it will provide a bridge.
commonly use sural nerve
Which type of nerve would have a better outcome...crushed or cleanly cut?
crushed, interestingly enough.
A glial scaffold of ECM left over after a nerve is cut is helpful in what?
in nerve regeneration...allows a nerve to sprout from a neighbor & innervate the muscle fiber that lost its nerve.
Why is CNS axon regeneration not the same as the PNS (not as successful)?
b/c removal of debris is slow
growth cones are upset & can hardly advance
astrocytes form a scar
What are some attractive adhesive markers in the CNS?
What are some attractive diffusible markers in the CNS?
What are some repellent adhesive markers in the CNS?
myelin-associated protein (ex: nogo)
What are some repellent diffusible markers in the CNS?
What's the deal with nogo?
it is a protein that is found in oligodendrocytes in the CNS.
Not found in Schwann cells in the PNS.
It is a myelin-associated protein & is repellent.
People think that if they can make an antibody to nogo then they can improve nerve regeneration in the CNS.
**one study showed that inhibiting it helps in spinal cord regeneration
Where does growth cone collapse often happen? Why?
often happens in the CNS b/c the oligodendrocytes don't help & then astrocytes move in.
Some people thought that putting a PNS nerve graft in the CNS would help with regeneration. Describe this experiment. Did it help?
Had problem with optic nerve.
put a sciatic nerve (PNS graft) in to connect the retinal ganglion cells to the superior colliculus. It helped!
**this showed that the real problem with CNS regeneration was the environment, not an intrinsic inability.
T/F Scientists have also studied trophic factors to help with nerve growth.
What is an example of optic nerve crush? What are some of the treatments that are considered for this?
ex: loss of retinal ganglion cells
use of growth factors
antibodies against myelin proteins
What happens in Parkinson's disease? WHat are some of the treatments that are considered?
loss of dopaminergic neurons in the substantia nigra
fetal tissue transplants
What happens in Alzheimer's? What are some of the treatments that are considered?
loss of cholinergic neurons in the basal forebrain
Treatments: growth factors--NGF, BDNF
What happens in amyotrophic lateral sclerosis (ALS)? What are some of the treatments that are considered?
loss of upper & lower motor neurons
growth factors: CNTF, BDNF, GDNF, IGF
What are some delivery method options for trophic factors?
Carrier-mediated Transport across BBB
Grafting of Cells Producing Trophic Factor
Development of Low-Molecular Weight Agonists
Fusion Proteins with Trafficking Motifs for Delivery along spinal/cranial Nerves
Is it true that some scientists are looking at ways to stop neuronal apoptosis to help with some of these diseases?
Why yes, it is true.
What are some strategies that researchers have been using to treat the loss of a specific neuron?
Drugs to enhance function of still remaining neurons
Trophic factors to rescue remaining neurons
Grafts (transplants) of embryonic or genetically engineered neurons to replace lost neurons
Stem cells to replace lost neurons
Prosthetic devices to replace function of lost neurons
What are some examples of drugs that are being used to enhance the function of still remaining neurons? What is the problem with this?
Alzheimer’s: AChE inhibitors
**only treats the symptoms, wears off in end stages as the neurons keep dying off.
What are some prosthetic devices that can be used to treat neuronal loss?
What are some problems that we run into with drug delivery to treat neuronal loss?
it may not be the trophic factor that is the problem...could be a problem with a receptor or even a downstream signal.
**it is important to not treat these things systemically as that causes side effects, but to instead treat it in a targeted manner.
What has the research shown with Grafts (transplants) of embryonic or genetically engineered neurons to replace lost neurons?
not working better than deep brain stimulation in Parkinson's patients
Is it even theoretically possible to integrate new neurons into someone's neuronal circuitry?
Mammals do it! With...Olfactory receptor cells; Taste receptor cells; Interneurons in olfactory bulb; Interneurons in hippocampus
Other vertebrates do it! With...Auditory and vestibular hair cells in birds; Retinal cells (including retinal ganglion cells) in fish; Song control neurons in forebrain of birds
What are the issues that you run up against with using stem cells to replace lost neurons?
risk of teratomas--try to make stem cells w/ a suicide gene if they get out of control.
not necessarily more successful that fetal grafts
HOw might stem cells be used for Parkinson's disease?
grow the cells in a dish
get out the dopaminergic neurons
place them in the striatum
What's the deal with the hair cells in the organ of Corti?
these cochlear hair cells can't regenerate in humans, but they can in birds.
we are only born with a certain number...
HOw do birds regenerate their auditory hair cells?
via stem cells
In humans...what can we do even tho we can't regenerate our cochlear hair cells?
we can get cochlear implants...run close to the cochlear nerve.
Which transcription factor are they researching to help out with regenerating hair cells?
What can you do for someone who has had some phrenic nerve damage?
well...the diaphragm's innervation is damaged & this can sometimes compromise breathing.
can use breathing pacemaker so that you don't have to be on a ventilator.
Describe the pressure sensitive prosthetic hand.
bionic hand can transmit sense of touch to the brain
this pressure sensation info is fed back into the stump of the median & ulnar nerves afferents.