Lecture 3 Study Questions Flashcards
What are typical conduction velocity ranges for human motor and sensory axons? How does CV scale with axonal diameter?
Motor and sensory axon conduction velocity can be as fast as 55 m/s and 60 m/s respectively. The conduction velocity scale states that for every 1um of axonal diameter, conduction velocity increases by 6 m/s.
How did Ramon y Cajal describe the nerve axon regeneration process in the PNS and in the CNS?
Ramón y Cajal hypothesized that nerve axons grew from their tip which he referred to as the growth cone. He hypothesized that in the PNS, guidance factors were necessary. He believed that the guidance factors were supplied by Schwann cells. He believed that something about the environment in the CNS made it impossible for axons to regrow. He proved this true by implanting peripheral axons into different parts of the brain, retina, and spinal cord.
What two mechanisms did Ramon y Cajal propose were needed to support successful regeneration?
Ramón y Cajal hypothesized that guidance factors were needed to support axonal regeneration. He also hypothesized the guidance factors were supplied by Schwann cells. Mechanical guidance and chemical guidance are two mechanisms thought to guide the nerve regeneration process. Other cells and/or proteins surrounding growth cones in the extracellular matrix provide mechanical guidance. Growth cones desire to make contact with these cells and proteins as they have cell adhesion molecules on their surface which promote nerve regeneration.
What are the three most common ways in which nerves can be mechanically injured?
Nerves can be compressed. Transient compression can result in no injury to the nerve. However, long term compression can cause damage to the axon.
Nerves can also be crushed which results in death to the distal end quite quickly.
Transection is when the nerve has been completely cut.
In an injured nerve, what happens to the axons proximal and distal to the injury? Why? How soon? For how long?
Distal to the injury, Wallerian degeneration occurs. This describes the degeneration of the distal axon.Postsynaptic neurons lacking input can degenerate ( Anterograde transneuronal degeneration).
Proximal to the injury, the stump of the damaged axon dies back until the next node of Ranvier. If the site of injury is quite close to the cell body, the neuron may die.
When the soma has been notified via retrograde transport that there is an injury, there is a reactivation of the genes involved in axonal growth during development. The expression of this gene results in increased protein synthesis. The proximal axon shrinks as the production of neurotransmitters is decreased during regeneration. As such, the cross sectional area decreases. The retrograde neuron’s terminals retract and the neuron degenerates due to deprivation of retrograde trophic factors (retrograde transneuronal degeneration).
The building materials synthesized by the soma will be brought to the growth cone via slow axoplasmic transport. The axon will regenerate at approximately 1 mm per day.
When the injured nerve is able to establish new connections, the lumen will increase as neurotransmitter production increases. The axon cross sectional area may return to its size pre-injury but it is often limited by fibrous growth and inflammation.
In an injured nerve, what happens to the myelin proximal and distal to the injury? Why? How soon? For how long?
Distal to the injury, myelin degenerates leaving behind endoneurial tubes called myelin ghosts. Myelin fragments and degenerating axons are removed by microglia if this was a central nervous system nerve injury or by macrophages if this was a peripheral nervous system injury.
Proximal to the injury, myelin is unaffected and its cross section remains the same.
What is the rate-limiting factor that determines the speed of nerve axon regeneration?
The rate limiting factor is the rate of slow anterograde transport which is approximately 1mm/day. This is because slow anterograde transport brings cytoskeletal elements, neurofilament & microtubule subunits to the growth cone.
What type(s) of injuries to peripheral nerves usually require surgical repair to enable a good outcome?
Transection injury: if the distal and proximal ends of the peripheral nerve are quite far apart. Surgical repair can enable a good outcome as it will bring the two ends closer together. Additionally, if the nerve is damaged by compression, removal of this compressed area and replacement with a donor nerve can lead to a good outcome.
If an injured nerve successfully regenerates and makes appropriate new connections, what happens to the axons proximal vs. distal to the injury site? Why? When? For how long?
After successful connection, the growing axon’s cross sectional area proximal to the injury will increase again. This is due to the increase in production of neurotransmitters as reconnection has occurred.
Note that the proximal axon’s lumen may return to its original value but can often be inhibited by fibrous tissue or inflammation.
What is a neuroma? Where does it develop? Why does it develop? Why is this often a problem?
Neuromas are tangled lingering sprouts of regenerating axons. Neuromas develop due as the body attempts to heal damaged nerve tissue. Instead of the axons reconnecting normally, they grow in a disorganized manner. They can develop at the site of nerve injury and regeneration. Neuromas are a problem as they are very painful. Free ending nerves attach to the neuromas causing pain. This affects patient quality of life and ability to complete activities of daily living.
What can surgeons do to prevent neuromas?
Tie up amputated nerve stumps to inhibit pointless axonal regeneration
Nerve grafts to guide nerve regeneration and prevent neuroma growth
What is known about guidance factors required for successful nerve regeneration?
Currently, researchers believe mechanical guidance and chemical guidance are two mechanisms thought to guide the nerve regeneration process. Other cells and/or proteins surrounding growth cones in the extracellular matrix provide mechanical guidance. Growth cones desire to make contact with these cells and proteins as they have cell adhesion molecules on their surface which promote nerve regeneration.
Neurotrophins, including nerve growth factor, are thought to serve as chemical guidance for successful nerve regeneration. Schwann cells produce neurotrophins.
What is a cable graft? What is the most common autograft donor tissue, and why? What are the advantages and disadvantages of this approach?
A cable graft is a type of nerve graft that involves using multiple nerve segments from a donor to form bundles in order to bridge the gap between severed ends of a nerve. The most common autograft donor tissue is the sural nerve as it has good diameter and length.
Nerve autografts are more advantageous than allografts or some artificial grafts as they are less likely to be rejected. As such, they can have higher success rates.
However,in order to collect the autograft, an additional surgical procedure is required in another location of the patient’s body. Additional invasive procedures increases the patient’s likelihood of developing an infection.
There are only a certain amount of suitable donor nerves that exist within a person’s body as well. Lastly, the site where the graft was taken is permanently denervated.
What are allografts? What are the advantages and disadvantages?
Allografts are grafts that are harvested from human cadavers. As the graft does not need to be harvested from the patient, this reduces the number of surgical procedures conducted on the patient. Allografts may be more suitable for large nerve repair procedures as there are only a finite amount of nerves that can be harvested from the patient for graftusage. Allografts also mean another site on the patient’s body isn’t denervated as a graft need to be harvested.
Allografts are more likely to be rejected as it is foreign tissue, leading to a lower success rate than autografts.
What other autologous tissues have been used?
Autologous blood vessels and muscle fibers and collagen tubes have been used as nerve healing conduits with varying success
