injury and repair of the NS Flashcards
what happens to information when a nerve breaks?
info is blocked and cant be transmitted
what is a primary lesion/injury?
where a nerve is cut
where can nerve damage spread to?
- anterograde degeneration - moving forward to the next synaptic bouton
- retrograde degeneration - moving backwards
- to the cell body
- through transneuronal degeneration
what is the endoneurium?
layer of c.t. around axons. Enclose and protect myelin and axons
what is the perineurium?
axons organised into fascicles. Perineurium is c.t. around a fascicle.
what is the epineurium?
outermost layer of dense c.t. Fasicles bundled together with blood supply and fatty acid tissue. These are surrounded by an epineural sheath.
what does the success of nerve repair depend on?
o The severity of the initial injury (primary damage):
- What has been damaged
-How much has been damaged
o The extent of secondary damage.
what is neurapraxia?
temporary loss of motor and sensory function due to blockage of nerve conduction
when does neurapraxia occur?
during ischaemia
what is damaged in neurapraxia?
myelin is disrupted
axon remains intact
does nerve degeneration occur in neurapraxia?
no
what is axonotmesis?
disruption of axons and myelin sheath damage resulting from severe crush or contusion.
what is damaged and what remains intact in axonotmesis?
Epineurium sheath as well as Schwann cells remain intact
Myelin and axon are damaged
is neurapraxia reversible?
yes
is axonotmesis reversible?
yes
why is axonotmesis reversible?
bc the epineurium is intact so the nerve still has a metabolic and blood supply
what is neurotmesis?
when both the axons and nerve sheath are disrupted
is neurotmesis reversible?
no
what is the most severe form of nerve injury?
neurotmesis
what is the least severe form of nerve injury?
neurapraxia
when is neuron damage reversible?
when the epineurium is intact, even if the axon is damaged
what are the 2 main things that happen after axon damage?
cell is alerted that damage has occurred
cells in the DRG change their phenotype
how is a cell alerted that damage has occured
a burst of APs sent to the DRG of axon
disruption of retrograde transport flow of trophic support
positive injury signals
what are neurotrophic factors?
factor that is associated with providing nourishment to allow for growth. Their expression (especially of the nerve growth factor) is increased when there is a nerve injury.
give examples of neurotrophic factors
Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF), Glial cell-Derived Neurotrophic Factor (GDNF)
what happens when cells in the DRG change their phenotype?
switch from transmission state to growth state
decrease in all ion channels and proteins involved in neurotransmission
upregulation in proteins involved in axonal growth to make new membranes
what does afferent terminal atrophy lead to?
loss of input to spinal cord –> disinhibition of neurons in the spinal cord –> spontaneous activity –> cell death
describe the process of nerve regeneration
- Schwann cells divide to make daughter cells in mitosis
- They secrete trophic factors to attract axons (guided back to the reconnection) and allow growth to happen.
- Daughter cells re-myelinate the axon after growth and make the new functional axon
what is the growth rate in the pns?
1mm/day
can vary between 0.5-0.9mm/day
why is it unusual for patients to regain normal functions?
the process of reconnecting various components is very complex
why is the outcome better when repair occurs earlier?
- Prolong axotomy = reduces the number of motor neurons and axons that can regenerate.
- After 1 month, Schwann cells down-regulate regeneration associated factors
what does prolonged denervation of muscles lead to?
o Muscle atrophy and fibrosis
o Profound decrease in numbers of regenerating axons through deteriorating intra-muscular sheath.
when is cns repair needed?
in spinal cord injury
what is tetraplegia?
total loss of all use of all 4 limbs and torso
what is paraplegia?
impairment in motor or sensory function of the lower extremities
what are the types of spinal cord trauma?
laceration
concussion
what does spinal cord trauma produce?
site of primary cell death - epicentre
what does the epicentre spread into?
zone of secondary cell death
how does a glial scar form?
after primary cns injury - macrophages and microglia engulf debris and the injury site becomes walled off by a glial scar
why is a glial scar good?
o Engulfs debris
o Seals the lesion site
o Repairs the BBB
how can a glial scar be a problem?
o Expresses chemicals that inhibit axon growth (chondroitin sulphate proteoglycans) – released by astrocytes –> acts as a physical and chemical barrier for neurodegeneration
explain what a sprouting response is?
axons will try and grow through glial scar but cannot go anywhere. Distal tracts will undergo Wallerian degeneration which will lead to lots of myelin debris and chemicals which inhibits axonal growth.
what are the two main barriers to cns repair?
hostile environment - glial scar and myelin-associated inhibitory proteins
- poor regenerative response
what is tinel’s sign used for?
used to identify sensory recovery –> lightly tapping over nerve to elicit sensation of tingling.
what procedures can be used to solve early problems with the cns?
neuroprotection - contains the effects of early trauma
promotion of axonal regeneration
guiding axonal regrowth
