Degeneration and Regeneration of Nerves* Flashcards
what are the variations by which efferent neurones supply effectors or other neurones?
Neurones supply skeletal muscles:
In the somatic Nervous System
Neurones supply smooth muscles:
In the autonomic Nervous System.
Smooth muscle is myogenic so it produce its own electrical activity - the nervous system simply modifies it (increase/decreases it)
Neurones supply Glands:
In the autonomic Nervous system
what are descending pathways?
the brain communicates with effectors of the somatic or autonomic divisions through chains of neurones called descending pathways in the 3 variations (1st flashcard)
what happens if a neuron’s environment is disturbed?
If a neurone or its immediate environment are disturbed , the neurone’s function might be disrupted
The extent of dysfunction and its longevity depends on the nature of the insult to the neurone and will therefore effect how the neurone communicates with its effector organ.
what are the layers that ensheath different parts of the nerve?
what layer would a superficial damage effect?
Epineurium (ensheaths entire nerve [adjacent fascicles])
Perineurium (ensheaths a nerve fascicle [collection of axons])
Endoneurium (ensheaths a single axon)
Myelin Sheath (ensheaths an Axon)
Most superficial damage with only effect the Epineurium.
As the damage is more severe you damage more of the above structures (in order).
what is Neuropraxis?
When a neurone temporarily loses its ability to function normally:
It is the temporary compression of the nerve fibre –> causing injury to the myelin sheath –> causing loss of function
Restoration of function would be complete upon recovery
Injury would be at the level of the myelin sheath only
Loss of function would be as a result of the disturbance to the myelin sheath only.
Pins and Needles are an example of Neuropraxis
Another example is Guillain-Barre Syndrome. It is antibody mediated damage of Schwann cell results in shorter internodes because of sequential remyelination. The accumulation results in onion bulb appearance.
what is Axonotmesis?
When the axons of a nerve together with their myelin sheaths are damaged whilst the endoneurium, perineurium and epineurium remain intact.
Axonotmesis is usually the result of over-stretching a nerve or due to a severe crush
Motor and sensory functions distal from the point of injury are completely lost over time.
what does Axonotmesis lead to?
This leads to Wallerian Degeneration:
It is due to restriction or loss of blood supply.
This is where the distal axonal skeleton disintegrates and the axonal membrane breaks apart. Also the myelin sheath breaks down.
You then get a phagocytic response to clean up debris at the site of injury.
Macrophages release mitogens that induce Schwann cells to divide and repopulate.
Schwann cells make laminin
Macrophages make interleukin, which induces Schwann cells to make Nerve Growth Factor – encourages distal axon to grow
The endoneurium, perineurium and epineurium provide guidance to the nerve sprouts as they spread looking for nerve growth factors.
If they reach the growth factors they continue to grow eventually reaching and reinnervating the target tissue.
Recovery of nerve function soon returns, and normal feeling and sensations can be restored.
what is Neurotmesis?
when the entire nerve fibre is completely severed.
Here the axon and the connective tissue of the nerve are all damaged
Occurs due to a severe contusion, stretch or laceration e.g. during a motorbike crash.
It is the most severe class of nerve damage according to Seddon’s Classification System
Complete recovery does not occur in such nerve injuries
It could result in the loss of sensation if a large number of sensory neurones are severed.
what is the treatment for nerve severance?
If your nerve is injured but not cut is will most likely heal.
However, if the nerve is completely severed the chances of healing are reduced.
Your surgeon can remove the damaged section and reconnect healthy nerve ends (nerve repair) or implant a piece of nerve from another part of your body (nerve graft).
These procedures can help your nerves to regrow.
What would be the fate of neurone A and neurone C is neurone B died?
what is the first thing to consider?
The behaviour of 3 classes of glial cells is critical for understanding this:
Myelin forming Cells
Oligodendrocytes (CNS)
Schwann Cells (PNS)
Astrocytes
Creates an environment in which neurones thrive,
They also have end feet on the cell bodies of other neurones, providing the neurones with nutrition
Their end feet form part the BBB.
Microglia
There are immune cells of the nervous system.
They can be in an activated state or a resting state. (different morphologies)
A neurone emits a signal which attracts microglial cells, they come and destroy kill the cells by puncturing their cell membranes.
What would be the fate of neurone A and neurone C is neurone B died?
what would be the fate minutes after injury is sustained?
The neurone will immediately produce lots of action potentials once it is damaged.
The neurone will then stop conducting action potentials beyond the site of injury
The two ends of the cut axon will be exposed and they will start leaking intracellular fluid, axonal transport (movement of intracellular organelles) occurs in both directions.
The cut end will soon pull apart, sealing themselves and swelling at the same time.
What would be the fate of neurone A and neurone C is neurone B died?
what would be the fate an hour after injury is sustained?
Synaptic terminal degenerates and you get an accumulation of neurofilaments and vesicles at the site of the terminal.
Astroglia surround the terminal, they react by causing terminals (behind and in front of the neurone) to be pulled away from postsynaptic cell.
What would be the fate of neurone A and neurone C is neurone B died?
what would be the fate days-weeks after injury is sustained?
Fate of the Proximal segment – the cell body will undergo chromatolysis
Fate of the Distal Segment – the distal stump of axon will undergo Wallerian Degeneration – you get attendance of astroglia.
what is the fate of the proximal segment of a divided axon?
Days after sustaining an injury, the proximal segment undergoes a process known as chromatolysis
The cell body soon becomes very active producing a lot of proteins for repairing the cell
The volume of the cell body increases (swelling) and it also becomes bloated with the newly synthesised products
The nucleus of the cell is consequently displaced from its central position to the peripheral margins of the cell body
The injured nerve soon seals (to stop fluid loss) the wounded stump to form a neuroma.
This segment of nerve does not die (except if the injury is very close to the cell body)
In some cases, the nerve stump soon regenerates to innervate peripheral structures
If the neurone dies the neurone connected to the divided neurone also undergoes retrograde trans neural degeneration and dies. (I.e. Neurone A dies if Neurone B dies)
If the neurone dies the post synaptic neurone undergoes transgrade trans-neural degeneration and dies. (I.e. If B dies C also dies.)
what is the fate of the distal segment of a divided axon?
The segment of the axon distal to the site of lesion is never viable
It soon dies (terminal degeneration) as a result of loss of nutritional support from the cell body
Thus the axonal segment undergoes Wallerian degeneration
The axon is digested by phagocytes
Tissues that might be preserved are
Myelin sheaths – when injured it produces signals which preserves other structures.
Epineurium, Perineurium and Endoneurium become a hollow tube to guide the proximal segment that has survived to allow regrowth of the axon.
what has degeneration of fibres and their targets helped for clinically?
Therefore, severing the axon causes degenerative changes in the injured neuron AND in the cells that have synaptic connections with the injured neuron.
Classically, degeneration of fibres and their targets has been used to trace neuronal circuits experimentally, and still is used to understand pathology post-mortem. E.g. cut one neurone and all the other neurones that die in the body must have been connected to that neurone.
how does regrowth of nerve supply to a muscle after denervation occur?
Re-growth of a nerve to re-supply a muscle or other target is known as ‘reinnervation’
Re-innervation of the original effector organ is often not always successful
Most nerves often re-innervate an effector organ that is different from its original target
This leads to emergence of all sorts of unexpected results (or syndromes) – Crocodile tears syndrome is an interesting example
what happens when an axon is cut?
When cut, the axons undergoes Wallerian degeneration. This axon may regrow past the site of injury
What will happen to the properties of the skeletal muscle when reinnervated by a different motor neurone subtype.
What is found the type FF muscle fibres switches it biochemistry and electrical properties to become Type S muscle fibre and vice versa. This confirms it is the alpha-motor neurone which influences the type of muscle fibres in the skeletal muscle.
what is Crushing Syndrome (Bywaters Syndrome) (compression syndrome)?
Crushing Syndrome: A severe, often fatal condition that follows a severe crushing injury particularly involving large muscle masses.
It is characterised by fluid and blood loss, shock, haematuria (blood in the urine), and renal failure..
In a nutshell it is TRAUMATIC RHABDOMYOLYSIS: crushing of the limbs, results influx of toxic myolytic products into the circulation
Reperfusion Injury:
As the injury has happened the blood supply is restored to damaged tissue.
The blood cleans up the site of injury and sweeps in toxic releases of the injury site in to the general circulation which could cause the death of the patient or kidney failure.
