Spinal Cord Injury Flashcards

1
Q

What is the leading cause of spinal injuries? Are males or females more often affected? Around what age?

A
  • vehicular accidents
  • males
  • under 30
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2
Q

What are some common problems caused by spinal cord injury?

A
  • paralysis and later muscle spasms
  • sensory deficits
  • neuropathic pain
  • autonomic dysreflexia
  • lack of bladder control
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3
Q

What indicates axonal growth after SCI?

A

growth cones

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4
Q

What are the different stages of SCI?

A
  1. primary injury
  2. spinal shock
  3. secondary injury
  4. scarring
  5. neuronal plasticity
  6. long term injury (spasms and pain)
  7. very long term continued loss of function
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5
Q

What are the events of spinal shock?

A
  • 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)

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6
Q

What is secondary damage of SCI caused by?

A
  • 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
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7
Q

What mainly forms the core of the scar after SCI? boundary?

A
  • boundary = astrocytes (proliferate at lesion)
  • core = pericytes (peel off capillary and make fibroblasts)
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8
Q

When do growth cones collapse during SCI?

A

early phase

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9
Q

Why can axons re-grow in the PNS?

A
  1. permissive environment: clean up of myelin and production of growth factors by Schwann cells
    (i.e. no Nogo)
  2. good intrinsic growth capacity: growth associated proteins in motoneuron, Gap43
  3. lack scar
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10
Q

Why can’t peripheral nerves be used for spinal cord repair?

A

by cutting and inserting the nerve in the spinal cord, you will create scar tissue

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11
Q

Why do growth cones collapse with myelin?

A

there is Nogo in myelin, and the axon has Nogo receptors

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12
Q

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?

A
  • NgR receptor on axon
  • Rho pathway
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13
Q

What are CSPGs? What is the function? Where are they found?

A
  • chondroitin sulphate proteoglycans
  • inhibit growth and plasticity
  • found on astrocytic scar and perineuronal net
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14
Q

Failure of regeneration can be caused by _______________ but also ________________________.

A

environment; lack of growth potential of neurons

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15
Q

Many central neurons hate to grow after injury, but ___________________ grow like neonatal cells. __________ neurons creep around the injury.

A

raphe neurons; 5HT

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16
Q

What causes failure of CNS regeneration after SCI?

A
  • 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)
17
Q

In development, myelin is ______________ after axon growth, whereas after injury myelin ___________ growth.

A
  • laid down
  • inhibits
18
Q

In the CNS after SCI, oligodendrocytes ____________________; microglia ____________________.

A
  • oligodendrocytes die and do not clean up debris
  • microglia clean up poorly
19
Q

Why is regeneration of CNS poor?

A
  1. non-permissive environment (myelin, lack of BDNF)
  2. poor capacity of neurons to grow (lack Gap43, cAMP, mTOR, PTEN)
  3. glial scar (astrocytes)
20
Q

What is the guiding principle of SCI treatment?

A

recapitulate development (i.e. repeat development, and enhance development molecules)

21
Q

Why is it important to halt plasticity early on?

A

the circuits might keep growing and create a complex mess

22
Q

What changes are considered synaptic plasticity?

A

CHANGES IN:
- synapse numbers
- dendritic spine shape
- receptor numbers and type (LTP)
- constitutive activity
- dendritic arborisation
- presynaptic inhibition

23
Q

What is the difference between regeneration and sprouting?

A
  • regeneration: growth from cut axon stump
  • sprouting: growth not at cut axon stump (above or below injury; on spared or lesioned axons)
24
Q

Interneurons act as a ___________ around injury.

A

relay

25
Q

What are some human examples of use-dependent plasticity?

A
  • braille readers
  • string instrument players
26
Q

What does enhanced physical activity promote?

A
  • upregulation of neurotrophic factors
  • neurogenesis
  • downregulation of receptor for myelin inhibitors
  • growth associated proteins (in neurons)
  • refinement of synaptic connectivity
  • blood flow, via neurovascular coupling
  • improved neuronal circuit function
27
Q

TRUE or FALSE: Donald Hebb discovered LTP, and Hubel and Wiesel discovered cortical plasticity.

A

TRUE

28
Q

TRUE or FALSE: autonomic dysreflexia causes spasms and decreased heart rate.

A

FALSE: spasms and increased heart rate

29
Q

Explain the plasticity of neurons below the injury.

A

SCI cuts brain-derived tonic drive to CPG, but training enables CPG neurons to be autonomously activated (neuronal plasticity).

i.e. there is a circuit below the injury

30
Q

TRUE or FALSE: the adult nervous system is malleable

A

TRUE

31
Q

What are key players in promoting sprouting after SCI?

A

activity and training

32
Q

What can we use to bridge the lesion site in SCI? Who first did this by using nerve grafts?

A
  • Schwann cells, olfactory ensheathing glia, stem cells
  • Albert Aguayo used nerve grafts
33
Q

What can stem cells do to repair SCI? Does it help injured or uninjured neurons?

A
  • remyelinate
  • provide neurotrophic support

i.e. help UNINJURED neurons

34
Q

Which inhibitors can be blocked by antibodies in SCI?

A

Nogo

35
Q

which enzyme can be used to digest scar tissue in SCI?

A

ChABC

36
Q

What is the main issue with promoting growth factors like BDNF after SCI?

A

BDNF also promotes pain

37
Q

How can we prevent the collapse of growth cones to treat SCI?

A

inactive the Rho pathway or increase cAMP