CNS Injury & Nerve Regeneration

Question 1

PNS or CNS can regenerate after damage?

Answer 1

PNS can regenerate after damage.

CNS can NOT regenerate after damage.

Question 2

What occurs during spinal cord injury?

Answer 2

• displacement of vertebral bones
• axons damaged, cannot conduct signals
• damaged neurons release glutamate –> electrotoxicity
• neurotrophin-deprived death
• swelling crushes longitudinal segments and damages white matter
• cytokines form glial scar
• glial scar inhibits regeneration
• myelin has inhibitory factors

Question 3

neurotrophin

Answer 3

• neuron growth factor
• allows neurons to survive (default w/o this is death)
• allows efficient synapses/paths to continue

-loss of axon transmission causes neurotrophin-deprived death

Question 4

what is the greatest source of cell death with a spinal cord injury?

Answer 4

Deprivation of neurotophin.

Question 5

what triggers formation of glial scar?

Answer 5

cytokines

Question 6

experimental strategies to repair spinal cord

Answer 6

Neuronal survival.
Altering terrain.
Role of inhibitors (inhibit the inhibitors).
Intrinsic capacity for regrowth.
Stem cell regenerative medicine.
Reconnection, training, synaptic plasticity.

Question 7

neuronal survival

Answer 7

experimental strategy to repair spinal cord

1) reduce swelling
- via methylpredisone
- surgical decompression (break vertebrae to alleviate swelling)
- hypothermia (slows events)

2) apply factors
- NGF
- BDNF
- NT3
- FGF
- artemin

3) engineered cells

Question 8

altering terrain

Answer 8

• embryonic grafts (PNS can regenerate, so graft it onto CNS)
• engineered bridges with collagen or secrete factors
• replace myelin and oligodendrocytes (myelin secretes inhibitory factors)
• show significant growth that stops the end of the permissive terrain

Question 9

inhibitor factors

Answer 9

• Nogo (neurons “no go”)
• MAG: myelin associated glycoprotein
• Receptor for Nogo/MAG: same receptor; if blocked it cripples motility by affecting cytoskeleton
• Rho: downstream signalling pathway

Question 10

what increases the intrinsic capacity for regrowth?

Answer 10

• GAP43
• tubulin
• actin

Question 11

stem cell regenerative medicine

Answer 11

• implant stem cells at site of damage
• cells can differentiate into neurons/glia, release BDNF (in animals)
• cannot control/optimize for differentiation
• clinical trial for safety/functional recovery

Question 12

reconnection, training, synaptic plasticity

Answer 12

• training paradigms to enhance regeneration (put legs on motorized bike pedals)
• can increase plasticity beyond site of damage and functional recovery
• debate over regeneration vs new sprouting; most likely new sprouting

Question 13

neuroengineering approaches

Answer 13

• pattern generators
• brain computer interface
• deep brain stimulation to reduce neuropathic pain
• computer controlled exoskeleton/robotics

Question 14

hope for clinical intervention

Answer 14

• combinational therapies not yet effective
• stem cell therapies, control over differentiation is promising approach
• promise of neuroengineering, robotics, pattern generators

Question 15

what factors exacerbate severity after spinal cord injury?

Answer 15

1) excitotoxicity
2) swelling w/i vertebral column
3) damage at one vertebral level interrupting transmission at all points below
4) subsequent loss of neurotrophins leading to cell death

Question 16

what interventions could enhance growth and reconnection after spinal cord injury?

Answer 16

1) preventing swelling (methylprednisone, crack vertebral column)
2) provide permissive substrate for growth
3) block myelin and glial scar based inhibitors
4) provide neurotrophins
5) adding local guideposts
6) stem cells
7) neuroengineering

Question 17

the majority of neuronal cell death occurs weeks after mechanical damage and is due to…

Answer 17

deprivation of neurotophins

Question 18

sequence of mechanical damage in spinal cord injury

Answer 18

1. small percentage of cells die
2. damaged neurons release glutamate
3. free radical formation leads to cell death
4. deprivation of neutrophins
5. largest percentage of neurons die