Lecture 18 - Spinal Cord Injury

Question 1

what causes spinal cord injuries?

Answer 1

mainly accidents (recreation, cars, motorbikes) –> mostly impacts males under 30

Question 2

what are the five most common types of spinal cord injury?

Answer 2

• compression
• contusion
• laceration
• stretching
• direct trauma (like gunshots)

Question 3

who was able to visually identify that axons initiate growth after injury?

Answer 3

Ramon y Cajal

Question 4

what are the six major stages of spinal cord injury and how long do they each last?

Answer 4

1) primary injury (immediate)
2) spinal shock (early - a few days to weeks)
3) secondary injury (early - days to weeks)
4) scarring (weeks)
5) neuronal plasticity (weeks to months)
6) long term injury

Question 5

what are some of the major hallmarks of long term spinal cord injury?

Answer 5

chronic inflammation, poor blood flow, and excess neuronal activity (spasms and pain)

Question 6

following spinal cord injury (SCI), most axons fail to regenerate and instead form large, swollen endings generically called:

Answer 6

retraction bulbs (signify aborted growth)

Question 7

spinal shock is associated with a:

Answer 7

lack of activity (reflexes very low)

Question 8

• loss of descending connections
• breakdown of membrane potentials
• Ca++ influx in cells
• loss of adequate blood flow
• loss of nutrients and oxygen (ATP drops)
• loss of neuromodulators (5-HT)
  these are all characteristics of:

Answer 8

spinal shock

Question 9

what are the eight major causes of secondary damage?

Answer 9

• ischemia
• iflammation/edemna
• glutamate and Ca++ toxicity
• BBB breakdown
• invasion of macrophages and cytokines
• activation of microglia and astrocytes
• free radicals
• secondary cell death

Question 10

death of cells outside of the site of injury

Answer 10

secondary cell death

Question 11

early scarring comes with:

Answer 11

secondary damage

Question 12

axons below the site of injury will be:

Answer 12

degenerated

Question 13

spinal cord injury scars are mainly formed by:

Answer 13

astrocytes (boundary) and pericytes (core)

Question 14

in the early phases of spinal cord injury there is inhibition of growth due to:

Answer 14

collapse of growth cones

Question 15

inhibition of neuronal growth comes from:

Answer 15

proteoglycans (perineuronal net) and myelin (Nogo)

Question 16

activation of inflammatory pathways like Sarm1 promote:

Answer 16

axon degeneration

Question 17

what type of degeneration occurs at the injury site?

Answer 17

Wallerian degeneration (leaves myelin debris)

Question 18

see slide 527

Answer 18

diagram good

Question 19

axonal regeneration is successful because of:

Answer 19

• permissive environment (clean up of myelin)
• good intrinsic growth capacity (growth associated proteins)
• lack of a scar

Question 20

can peripheral nerves be used for spinal cord repair?

Answer 20

not really, once the nerve tries to re-enter the injury site, the environment becomes non-permissive to growth (slide 531)

Question 21

the growth cone collapses with:

Answer 21

myelin (something in myelin is inhibitory)

Question 22

what discovered the role of myelin in the CNS?

Answer 22

Martin E Schwab

Question 23

found on the astrocytic scar and the perineuronal net, and inhibit growth and plasticity (physical and chemical barrier)

Answer 23

chondroitin sulphate proteoglycans (CSPGs)

Question 24

failure of regeneration is caused by environmental factors, but also:

Answer 24

lack of growth potential of neurons

Question 25

what can stem cells do?

Answer 25

have the potential to grow into the white matter

Question 26

in development, myelin is laid down ____ axonal growth, whereas after injury myelin ____ axonal growth

Answer 26

after, inhibits

Question 27

unlike schann cells, oligodendrocytes:

Answer 27

die and do not clean up debris

Question 28

unlike schwann cells, microglia:

Answer 28

clean up poorly

Question 29

list three factors that cause poor axonal regeneration

Answer 29

- non permissive environment (myelin, lack of BDNF) - poor capacity of neurons to grow - glial scar (astrocytes)

Question 30

what is the guiding principle of spinal cord injury treatment?

Answer 30

recapitulate development

Question 31

surviving neurons can change through:

Answer 31

plasticity

Question 32

list six major changes in neurons that contribute to synaptic plasticity

Answer 32

- synapse numbers - dendritic spine shape - receptors numbers and type - constitutive activity - dendritic arborisation (branching out at the end of a nerve fiber) - presynaptic inhibition

Question 33

growth from a cut axon stump

Answer 33

axonal regeneration

Question 34

growth from anywhere but the cut axon stump

Answer 34

axonal sprouting

Question 35

interneurons act as a _____ around injury

Answer 35

relay

Question 36

what are two examples of use-dependent plasticity that occur naturally in the brain?

Answer 36

- Braille readers - string instrument players

Question 37

enhanced physical activity promotes:

Answer 37

- upregulation of neurotrophic factors - neurogenesis - downregulation of receptors for myelin inhibitors - growth associated proteins - refinement of synaptic activity (?) - blood flow (via neurovascular coupling) - improved neuronal circuit function

Question 38

Donald Hebb is credited for discovering:

Answer 38

LTP

Question 39

Hubel and Wiesel are credited for discovering:

Answer 39

cortical plasticity

Question 40

neurons that fire together:

Answer 40

wire together

Question 41

does treadmill training help with recovery from spinal cord injury?

Answer 41

yes

Question 42

spinal cord injury (SCI) cuts brain derived tonic drive to _____, but training enables _____ to be autonomosly activated (neuronal plasticity)

Answer 42

the central pattern generator, CPG

Question 43

bridging the lesion site was first done by ____ using nerve grafts

Answer 43

Albert Aguayo

Question 44

injection of stem cells into the site of injury has the potential to:

Answer 44

help remyelinate and provide neurotrophic support to SCI injuries

Question 45

one treatment currently in clinical trials is to apply antibodies to block:

Answer 45

inhibitors on their receptors (tested for Nogo on oligodendrocytes)

Question 46

a treatment for SCI that involves digesting the scar using:

Answer 46

the enzyme condroitinase (ChABC) --> want to inject it locally

Question 47

go review slides 567-570

Answer 47

how on earth does a girl write that down