Wk5 Degeneration And Regeneration Of Peripheral Nerves Flashcards
Pathways of actions through nervous system
• Skeletal muscles – via the somatic Nervous System • Smooth muscles – via the autonomic Nervous System • Glands – via the autonomic Nervous System
Permutations By Which Efferent Neurones Supply Effectors or Other Neurones
• In all these cases, the brain communicates with effectors of the somatic or autonomic divisions through relay chains of neurones that we call descending pathways
• Causes for degeneration of nerves are multiple
– Acquired causes through injury
– Genetics of the body
– Natural processes of aging
– etc
• Injured peripheral nerves have a capacity to regenerate and re-
innervate effectors
• CNS neurones do not regenerate as readily
Structural Features of The Neurone Likely To Be Affected by Insult
Epineurium (superficial) • (ensheaths the entire nerve) • (interfascicular bands attach adjacent nerve fascicle) Perineurium • (ensheaths a nerve fascicle) • (a fascicle is a collection of axons) Endoneurium • (ensheaths a single cell’s axon) Myelin Sheath Axon (deepest)
Neuropraxis
• When a neurone temporarily loses its ability to function normally, this is known as neuropraxis –
– Injury would be most probably at the level of the myelin sheath only
• e.g. Temporary compression of the nerve fibre leading to loss of blood supply
– Restoration of function would be complete, upon recovery
Axonotmesis
• Axonotmesis is usually as a result of a severe crush injury to a peripheral nerve
• Axons of a nerve together with their myelin sheaths are damaged
• The endoneurium, perineurium and epineurium remain intact.
- breaks axons up
- Motor and sensory nerves are affected in the same way
- If endoneurium, perineurium and epineurium are intact, new nerve sprouts would use guidance cues from tubes of the ensheathing membranes to re-supply the target effector (or affector) to restore normal function of injured nerve.
- Restoration of function can be expected to return fully
Neurotmesis
• When the entire nerve fibre is completely transeceted or severed this is known as neurotmesis
- It is the most severe class of nerve damage according to Seddon’s Classification System
- The axon and the connective tissue of the nerve are all damaged
- Recovery of function does not occur in such nerve injuries
Reactions To Injury Within A Damaged Neurone
• When a nerve is injured, it is often said to be divided into 2 segments
– Proximal Segment
• Likely to continue to receive support of
cell body
– Distal Segment
• Often cut off from cell body
• Loses potential for repairs
• Loses potential for nutritional support
• Becomes vulnerable to phagocytosis by glia
- further away from cell body the proximal segment will survive but distal unlikely
When Neurones Are Injured, How Does Their Local Environment Change?
• The behaviour of 3 classes of glial cells is critical
• Myelin Forming Cells – Oligodendrocytes – Schwann Cells
• Astrocytes
– Create an environment in which neurones thrive
• Microglia
– These are immune cells of the nervous system
Minutes after injury is sustained
Minutes After Injury is Sustained
The neurone will immediately 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 occurs in both directions
The cut ends will soon pull apart, sealing themselves and swelling at the same time
An hour after surgery
• Synaptic terminal degenerates - accumulation of neurofilaments, vesicles
• Astroglia surround terminal normally
– They react by causing terminals to be
pulled away from postsynaptic cell
Wound is sealed
Fate of The Distal Segment of A Severed Nerve
• The segment of the axon distal to the site of lesion is never viable
• It soon dies 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
– Epineurium
– Perineurium
– Endoneurium
• These form hollow tubes to guide any new regrowth of the end of the proximal end
Days to week following injury
• The Distal Segment stump of axon will undergo Wallerian Degeneration (i.e. digested by phagocytes) - phagocytosis
Fate of The Proximal Segment of A Severed Nerve
• 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 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 the wounded stump to form a neuroma
• This segment of nerve does not die
• In some cases the nerve stump soon regenerates
to innervate peripheral structures
Fate of Axonal Stump on Proximal Segment of Axon
Regenerating axons form many sprouts, some of which find Schwann cell tubes
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 fibers and their targets
has been used to trace neuronal circuits experimentally, and still is used to understand pathology post-mortem
The Fate of A Denervated Muscle That is Not Reinnervated - acute phase
• The muscle is immediately paralysed – In this case, flaccid paralysis • The muscle will become areflexic • The muscle will start to fasciuculate • If the muscle is not reinnervated, the fasciculations will subside
