Neuroplastic Responses

Question 1

What are 4 types of neuroplastic responses to nervous system damage?

Answer 1

• Neural degeneration
• Regeneration
• Reorganization
• Recovery

Question 2

What is neural degeneration?

Answer 2

• Deterioration and death of neurons

Question 3

When is neural degeneration common?

Answer 3

• Common in neurodevelopment

- Common in neurodegenerative diseases

Question 4

What affects the onset of neural degeneration?

Answer 4

• Type of neurons
• Pathologies (ex. Alzheimer’s vs. Parkinson’s)
• Modulated by glial cells
• Modulated by activity of affected neurons (‘use it or lose it’)

Question 5

What is a model for neural degeneration?

Answer 5

• Axotomy (cutting axons)
• > Always: anterograde (rapid) degeneration of distal segment b/n cut and synaptic terminals
• > Often: retrograde (slow) degeneration of proximal segment b/n cut and cell body
• > Sometimes: Transneuronal degeneration of neurons connected to damaged neurons (can be anterograde or retrograde)

Question 6

What is neural regeneration?

Answer 6

• The regrowth of damaged neurons
• Common and very precise in invertebrates and ‘lower’ vertebrates (ex. frogs, geckos)
• Not observed in CNS of ‘higher’ vertebrates
• Observed in PNS of ‘higher’ vertebrates, but uncommon (ex. lizard will grow tail back)

Question 7

Which type of cells promote regeneration? How?

Answer 7

• Schwann cells (PNS)
• Clean up cellular debris of degeneration
• Neurotrophic factors stimulate growth
• CAMs provide a pathway

Question 8

What inhibits regeneration? How?

Answer 8

• Oligodendroglia
• Do not clean up cellular debris
• Do not release neurotrophins and CAMs
• Release factors that inhibit regeneration

Question 9

What is collateral sprouting?

Answer 9

• Nearby neuron grows collaterals to innervate post-synaptic cell of killed neuron to keep it alive

Question 10

How many patterns of axonal regeneration are there in mammalian peripheral nerves?

Answer 10

3

Question 11

What is neural reorganization? What drives reorganization?

Answer 11

• Experience drives plastic brain organization/reorganization
• Damage too induces reorganization (peripheral or cortical damage)

Question 12

What is an example of neural reorganization?

Answer 12

• Retinotopic cortical maps after retinal lesions
• Cortical areas acquired new receptive fields
• Similar changes observed in minutes after retinal lesion in monkeys

Question 13

What happens to the organization of the somatosensory cortex 10 years after an arm amputation?

Answer 13

• Arm area of somatosensory cortex was processing input from face
• Massive cortical reorganization

Question 14

Describe the reorganization of the motor cortex after motor neuron transection?

Answer 14

• A few weeks after vibrissae denervation, the motor cortex for the vibrissae stimulated other facial muscles (moves areas other than whiskers)

Question 15

Does cortical reorganization happen in humans too?

Answer 15

YES

• After brain damage
• ex. in blind people,
• > increase in auditory and somatosensory cortices
• > Auditory and somatosensory cortices take over formerly visual cortex
• > Enhanced auditory and somatosensory mediated skills

Question 16

What is the 2-step model of reorganization?

Answer 16

• Strengthened existing connections due to a release from inhibition
• > consistent with speed and localized nature of reorganization
• Establishment of new connections via collateral sprouting
• > magnitude can be too great to be explained by changes in existing conditions

Question 17

Describe the recovery of function after CNS damage?

Answer 17

• Post damage improvements are common
  Includes:
• Improvements NOT due to true recovery
• True recovery

Question 18

What are some improvements not due to true recovery?

Answer 18

• Reduction of initial insult (e.g. edema; can be removed immediately)
• Compensatory changes via new learning (do things differently)
• Compensatory changes via cognitive reserve (old learning; previous high function = better)

Question 19

What happens in true recovery?

Answer 19

• Collateral growth
• Neuroplastic changes in undamaged tissue
• Neurogenesis from stem cells (happens in at least 2 locations)

Question 20

Where is increased neurogenesis seen after stroke damage?

Answer 20

• Dentate gyrus (in hippocampus)

Question 21

What are 3 ways to treat nervous system damage?

Answer 21

• Neurotransplantation (embryonic or nonembryonic cells)
• Neuroprotective treatments
• Rehabilitative training

Question 22

What are 2 examples of neurotransplantation of embryonic cells?

Answer 22

• Neurotransplant of fetal substantia nigra cells for Parkinson’s disease
• > successful in MPTP monkey model
• > Limited success with humans (immune response)
• Neurotransplant of fetal stem cells for spinal cord damage
• > improved mobility in rats

Question 23

What are 3 examples of neurotransplantation of nonembryonic cells?

Answer 23

• Adrenal medulla autotransplantation for Parkinson’s disease
• > ineffective (hard for adult neurons to make new connections)
• Transplant of glial cells promoted axonal regeneration in the spinal neurons of rats
• > Schwann cells or olfactory ensheathing cells
• Autotransplantation of olfactory ensheathing cells promoted regeneration in spinal cord and some recuperation of function in 3 patients w/ spinal cord injury

Question 24

What are some neuroprotective treatments?

Answer 24

• Apoptosis inhibitor protein
• > reduced neuronal loss and learning impairments in rats
• Neurotrophins
• > Block degeneration of damaged neurons

Estrogens
-> Limit or delay neuronal death

Question 25

What can rehabilitative training be used for (4)?

Answer 25

- Treating Strokes - Treating Spinal injury - Benefits of cognitive/physical exercise - Treating phantom limbs

Question 26

How can rehabilitative training be used to treat strokes?

Answer 26

- Monkeys recovered hand function and had smaller brain damage from induced strokes following rehab training - Constraint-induced therapy: tie down functioning limb while training the impaired one

Question 27

What is an example of rehabilitative training to treat spinal injury?

Answer 27

- Facilitated walking (harness on treadmill) - Hopefully do not lose more function - Maybe regain some function - Maintenance of a high degree of plasticity makes this possible

Question 28

What are some benefits of cognitive and physical exercise?

Answer 28

- Active people seem neuroprotected - Rodents raised in enriched environment are resistant to induced neurological conditions - Physical activity alone improves brain in rodents (neurogenesis, learning, aging, etc)

Question 29

How can rehabilitative training be used to treat phantom limbs?

Answer 29

- Phantom limb feeling comes from brain, not limb (still perceives image of limb) - Amputee can get pain relief with visual feedback (e.g. use a mirror, move non-amputated limb to move mental representation out of uncomfortable position) - Virtual reality (e.g. electrodes in muscles, think to move amputated limb on screen)

Question 30

What is Ramachandran's hypothesis?

Answer 30

- Phantom limb is caused be reorganization of the somatosensory cortex following amputation

Question 31

Strokes are caused by what?

Answer 31

- Cerebral hemorrhage | - Cerebral ischemia

Question 32

Describe two regions where damage occurs in strokes.

Answer 32

- Infarct and penumbra

Question 33

What role does glutamate play in strokes?

Answer 33

- Excessive glutamate released kills post-synaptic cells - Causes excitotoxicity - chain of reactions to spread activity

Question 34

How might one limit the extent of damage by glutamate during a stroke?

Answer 34

- Add glutamate antagonists

Question 35

If the amyloid hypothesis is correct, what would you expect of anti-amyloid immunotherapy in humans? What would you expect if this hypothesis is not correct?

Answer 35

CORRECT - Less amyloid and less tau - Decreased damage - Reduction in symptoms INCORRECT - Eliminate amyloid plaques, NOT tau proteins - Would not improve cognitive impairments