Neuronal Injury Flashcards
most injuries to the nervous system affect the ____
axon
what can affect nerves in the PNS or CNS?
physical trauma
vascular insufficiency (stroke)
metabolic disorders
tumours
injury to the axon divides the neuron into ____ and ____
- proximal portion: retains attachment to cell body
- distal fragment
what is a lesion?
impact on function
chromatolytic reaction
proximal part of axon:
- eccentric nucleus (floats to one end)
- nissl substance fragmentation
- ^RNA and protein synthesis
- changes in expression of neuron’s genes
wallerian degeneration
distal segment of injured axon:
- axonal degeneration
- myelin sheath fragmentation
- axonal & myelin debris is enveloped & destroyed by microglia
transneuronal anterograde degeneration
postsynaptic neuron affected due to lack of input (NT) and eventually atrophies and dies depending on extent of neuronal damage
transneuronal retrograde degeneration
synaptic stripping
neuron that provides injured cell with input:
synaptic space increases and is interrupted by glial processes (schwann cells in PNS; astrocytes/microglia in CNS)
____ neurons have higher capacity to regenerate
peripheral neurons
____ elements survive in the distal fragment of the axotomized neuron
connective tissue elements
regeneration
the proximal fragment grows ____ that are guided to the distal portion by chemotropic factors secreted by _____
axonal sprouts; schwann cells
regeneration process
- proximal fragment grows axonal sprouts guided to the distal portion by chemotropic factors secreted by schwann cells
- axonal growth is promoted and regenerated axons find their targets
frey’s syndrome
regenerated axons guided to inappropriate targets
what happens if axonal sprouts do not make contact with distal element?
axonal sprouts become entangled and form a benign mass (neuroma)
factors contributing to decreased capacity of CNS neurons to regenerate
- schwann cells
- inhibiting factors
- intrinsic differences
- scarring & inflammation
regeneration in PNS vs CNS
schwann cells
PNS:
- schwann cells produce growth promoting factors to promote axonal growth
- in embryo, both CNS & PNS nerves promote growty, only PNS retains ability
CNS: oligodendrocytes inhibit axonal growth in CNS
regeneration in PNS vs CNS
inhibiting factors
- both PNS & CNS secrete growth promoting factors
- CNS also contains inhibiting factors
- central myelin = potent axonal growth inhibitor (CNS myelination occurs after growth is complete)
regeneration in PNS vs CNS
intrinsic differences
CNS cells express proteins that render them less able to regenerate after initial formatting stages
regeneration in PNS vs CNS
scarring & inflammation
in CNS injury:
- scar formation
- astrocyte proliferation
- microglia & other immune cell recruitment
- inflammation
if surrounding tissues are selectively excluded, healing is enhanced
clinical considerations for regeneration
- introduction of trophic substances
- schwann cell grafts
- introduction of antibodies against axonal growth inhibitors
- transplantation of fetal tissue
- administration of immunosuppressants, anti-inflammatory steroidal agents
