Lecture 18 - Spinal Cord Injury Flashcards
what causes spinal cord injuries?
mainly accidents (recreation, cars, motorbikes) –> mostly impacts males under 30
what are the five most common types of spinal cord injury?
- compression
- contusion
- laceration
- stretching
- direct trauma (like gunshots)
who was able to visually identify that axons initiate growth after injury?
Ramon y Cajal
what are the six major stages of spinal cord injury and how long do they each last?
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
what are some of the major hallmarks of long term spinal cord injury?
chronic inflammation, poor blood flow, and excess neuronal activity (spasms and pain)
following spinal cord injury (SCI), most axons fail to regenerate and instead form large, swollen endings generically called:
retraction bulbs (signify aborted growth)
spinal shock is associated with a:
lack of activity (reflexes very low)
- 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:
spinal shock
what are the eight major causes of secondary damage?
- ischemia
- iflammation/edemna
- glutamate and Ca++ toxicity
- BBB breakdown
- invasion of macrophages and cytokines
- activation of microglia and astrocytes
- free radicals
- secondary cell death
death of cells outside of the site of injury
secondary cell death
early scarring comes with:
secondary damage
axons below the site of injury will be:
degenerated
spinal cord injury scars are mainly formed by:
astrocytes (boundary) and pericytes (core)
in the early phases of spinal cord injury there is inhibition of growth due to:
collapse of growth cones
inhibition of neuronal growth comes from:
proteoglycans (perineuronal net) and myelin (Nogo)
activation of inflammatory pathways like Sarm1 promote:
axon degeneration
what type of degeneration occurs at the injury site?
Wallerian degeneration (leaves myelin debris)
see slide 527
diagram good
axonal regeneration is successful because of:
- permissive environment (clean up of myelin)
- good intrinsic growth capacity (growth associated proteins)
- lack of a scar
can peripheral nerves be used for spinal cord repair?
not really, once the nerve tries to re-enter the injury site, the environment becomes non-permissive to growth (slide 531)
the growth cone collapses with:
myelin (something in myelin is inhibitory)
what discovered the role of myelin in the CNS?
Martin E Schwab
found on the astrocytic scar and the perineuronal net, and inhibit growth and plasticity (physical and chemical barrier)
chondroitin sulphate proteoglycans (CSPGs)
failure of regeneration is caused by environmental factors, but also:
lack of growth potential of neurons
what can stem cells do?
have the potential to grow into the white matter
in development, myelin is laid down ____ axonal growth, whereas after injury myelin ____ axonal growth
after, inhibits
unlike schann cells, oligodendrocytes:
die and do not clean up debris
unlike schwann cells, microglia:
clean up poorly
list three factors that cause poor axonal regeneration
- non permissive environment (myelin, lack of BDNF)
- poor capacity of neurons to grow
- glial scar (astrocytes)
what is the guiding principle of spinal cord injury treatment?
recapitulate development
surviving neurons can change through:
plasticity
list six major changes in neurons that contribute to synaptic plasticity
- synapse numbers
- dendritic spine shape
- receptors numbers and type
- constitutive activity
- dendritic arborisation (branching out at the end of a nerve fiber)
- presynaptic inhibition
growth from a cut axon stump
axonal regeneration
growth from anywhere but the cut axon stump
axonal sprouting
interneurons act as a _____ around injury
relay
what are two examples of use-dependent plasticity that occur naturally in the brain?
- Braille readers
- string instrument players
enhanced physical activity promotes:
- 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
Donald Hebb is credited for discovering:
LTP
Hubel and Wiesel are credited for discovering:
cortical plasticity
neurons that fire together:
wire together
does treadmill training help with recovery from spinal cord injury?
yes
spinal cord injury (SCI) cuts brain derived tonic drive to _____, but training enables _____ to be autonomosly activated (neuronal plasticity)
the central pattern generator, CPG
bridging the lesion site was first done by ____ using nerve grafts
Albert Aguayo
injection of stem cells into the site of injury has the potential to:
help remyelinate and provide neurotrophic support to SCI injuries
one treatment currently in clinical trials is to apply antibodies to block:
inhibitors on their receptors (tested for Nogo on oligodendrocytes)
a treatment for SCI that involves digesting the scar using:
the enzyme condroitinase (ChABC) –> want to inject it locally
go review slides 567-570
how on earth does a girl write that down
