Spinal Cord Injury Flashcards
(37 cards)
What is the leading cause of spinal injuries? Are males or females more often affected? Around what age?
- vehicular accidents
- males
- under 30
What are some common problems caused by spinal cord injury?
- paralysis and later muscle spasms
- sensory deficits
- neuropathic pain
- autonomic dysreflexia
- lack of bladder control
What indicates axonal growth after SCI?
growth cones
What are the different stages of SCI?
- primary injury
- spinal shock
- secondary injury
- scarring
- neuronal plasticity
- long term injury (spasms and pain)
- very long term continued loss of function
What are the events of spinal shock?
- loss of descending connections
- break down of membrane potentials
- Ca influx –> cytotoxicity
- loss of good blood flow
- loss of nutrients and O2 –> ATP drops
- loss of neuromodulators (5HT)
(i.e. lack of activity)
What is secondary damage of SCI caused by?
- ischemia
- inflammation, edema
- glutamate and calcium toxicity
- BBB breakdown
- invasion from macrophages and immune system related cytokines
- activation of microglia and astrocytes (scarring and reduced plasticity)
- free radicals
- secondary cell death
What mainly forms the core of the scar after SCI? boundary?
- boundary = astrocytes (proliferate at lesion)
- core = pericytes (peel off capillary and make fibroblasts)
When do growth cones collapse during SCI?
early phase
Why can axons re-grow in the PNS?
- permissive environment: clean up of myelin and production of growth factors by Schwann cells
(i.e. no Nogo) - good intrinsic growth capacity: growth associated proteins in motoneuron, Gap43
- lack scar
Why can’t peripheral nerves be used for spinal cord repair?
by cutting and inserting the nerve in the spinal cord, you will create scar tissue
Why do growth cones collapse with myelin?
there is Nogo in myelin, and the axon has Nogo receptors
Which receptor on the axon do inhibitory factors (like Nogo) in the myelin have to act on? This leads to activation of which pathway that causes growth cone collapse?
- NgR receptor on axon
- Rho pathway
What are CSPGs? What is the function? Where are they found?
- chondroitin sulphate proteoglycans
- inhibit growth and plasticity
- found on astrocytic scar and perineuronal net
Failure of regeneration can be caused by _______________ but also ________________________.
environment; lack of growth potential of neurons
Many central neurons hate to grow after injury, but ___________________ grow like neonatal cells. __________ neurons creep around the injury.
raphe neurons; 5HT
What causes failure of CNS regeneration after SCI?
- CNS myelin inhibits growth (Nogo, Mag)
- scar tissue represents mechanical and chemical barrier (proteoglycans)
- perineuronal net
- lack of adeqyate growth factors (BDNF)
- neuronal growth potential poor (normally helped by intracellular cAMP, mTOR, PTEN levels)
In development, myelin is ______________ after axon growth, whereas after injury myelin ___________ growth.
- laid down
- inhibits
In the CNS after SCI, oligodendrocytes ____________________; microglia ____________________.
- oligodendrocytes die and do not clean up debris
- microglia clean up poorly
Why is regeneration of CNS poor?
- non-permissive environment (myelin, lack of BDNF)
- poor capacity of neurons to grow (lack Gap43, cAMP, mTOR, PTEN)
- glial scar (astrocytes)
What is the guiding principle of SCI treatment?
recapitulate development (i.e. repeat development, and enhance development molecules)
Why is it important to halt plasticity early on?
the circuits might keep growing and create a complex mess
What changes are considered synaptic plasticity?
CHANGES IN:
- synapse numbers
- dendritic spine shape
- receptor numbers and type (LTP)
- constitutive activity
- dendritic arborisation
- presynaptic inhibition
What is the difference between regeneration and sprouting?
- regeneration: growth from cut axon stump
- sprouting: growth not at cut axon stump (above or below injury; on spared or lesioned axons)
Interneurons act as a ___________ around injury.
relay
