Neuronal Repair Flashcards
What are the immediatechanges to neurons in the PNS after damage
- Cell body will change shape
- Ribosomes stop working (chromolysis/chromatolysis) loss of Nissl substance
- Nucleus will move to the side
- Wallerian Degeneration
- Muscle now has lost input and will begin to atrophy
What is Wallerian Degeneration?
§ Will have degeneration of axon and mylein sheath below site of injury
§ Debris will be removed by macrophages
What is the typical response to injury 3 weeks post in PNS
- Nucleus will move back to centre again
- Schwann cells prolifferate forming a compact cord
- Growing axons will then penetrate into the schwann cell cord at around 0.5-3 mm/day
§ Some wont be effective at penetrating - No guarantee that the axon will grow in its original path
- Has the possibility that it will miss the schwann cell cord and can cause neuroma,
§ Can be quite painful
How does the PNS injury resolve
Neurons/Axon will reform at the neuromuscular junction and electrical activity will be reformed and muscle can now contract
What effect does PNS cut or crush have on regeneration
- If the nerve was crushed then higher level of axon growht in the correct direction
- If the nerve was cut then the axonal growth has less chance of growing in the correct division and will be less guided
What factors complicate CNS regrowth compared to PNS
- Very complex circuitry
- Are very localised to a particular region
- Different types of neurons, different layers of neurons, different tracts
- Hence direction is very important
- Circuitry is very important
- Astrocyte gliosis scarring can form a barrier to prevent regrowth
Difference of oligodendrocytes compared to schwann cells in regrowth
Oligo are inhibitory to regrowth whereas schwann will promote regrowth
Typical lesion that causes neuron lesion in CNS and treatment
Ischemic Stroke and streptokinase
Secondary effects to stroke
§ Ischemia § Ca2+ influx § ROS production/membrane breakdown § Glutamate release for increased excitibility and can be further lethal to neurons § BBB breakdown
What is the typical pathogensis to neuronal damage in the CNS
§ Microglia cells will infiltrate due to injury
§ This will then lead to ongoing axonal degeneration
§ Demyleination
§ Apoptosis
§ Further loss of other neurons
§ There is also astrocyte glioisis and a glial scar is formed
§ In some injuries a cavity (fluid filled) will form to also inhibit growth
§ Meningeal fibroblast regeneration
4 main areas of treatment
Neuroprotection, axonal regeneration and functional integration, modulation of astrocytic gliosis and neural stem cell transplants
What factors need to be overcome to prevent axonal regeneration and functional integration
To increase the presence of trophic factors to promote axonal plasticity (compensation by other nerves) and axon regeneration and to prevent the formation of glial scaring
How is gliosis regulated by astrocytes
- Upregulation of astrocyte cytoskeleton proteins such as GFAP
- Hypertrophic - cell body is larger
- Proliferate
- Interdigitate processes to produce barrier
- Can secrete extracellular matrix which is very inhibitory for regrowth
- Can secrete developmental axon guidance molecules
- Can form a scar which axons are unable to pass through
Approaches to stop gliosis
- Blocking ECM secreation
- Knock out mice for certain genes regulating astrocyte activity - Stopping the expression of Myelin inhibitors and axon guidance molecules that inhibit growth - Modulation of cell membrane proteins that guide axon growth such as EphA4 and ephrinA5
Some approaches to inhibit mylein inhibitors and axon guidance molecules
- Myelin inhibitors and axon guidance molecules that inhibit regrowth
(If these factors can be removed can axon growth be promoted)
§ These factors bind to the nogo receptor and this activates the Rho pathway to inhibit axon growth
