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NAB > 2o. Brain Repair - CNS > Flashcards

2o. Brain Repair - CNS Flashcards

1
Q

2 Drawbacks of the Functional Specialisation of the Brain

A
  • Proliferative inability

- Irreversibility of intra-protoplasmic differentiation

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2
Q

2 Types of CNS Injury

A
  • Ischaemic injury

- Neurodegenerative disease

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3
Q

Ischaemic Injury

A

Excitotoxic

Increased intracellular [Ca2+] that damages or kills neurones

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4
Q

3 Neurodegenerative Diseases

A
  • Parkinson’s disease
    Alzheimer’s disease
    Multiple Sclerosis
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5
Q

Methods of Treating CNS Neurone Loss

A
  • Delaying neurone loss

- Replacing lost neurones

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6
Q

Delaying Neurone Loss

A

Neuroprotection using:

  • NMDA receptor blockers
  • Neurotrophic factors

Trialed in neurodegenerative disease

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7
Q

Replacing Lost Neurones

- 3 Methods

A
  • Neural Grafting
  • Neural Stem Cells
  • Stem cell grafting
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8
Q

Neural Grafting

- Mechanism

A

Grafting petal brain cells into the damaged brain

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9
Q

Neural Grafting

- Uses

A

Parkinson’s disease

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10
Q

Neural Grafting

- Parkinson’s Disease Method

A

Grafting fetal substantia nigra cells into the striatum to replace dopamine

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11
Q

Neural Grafting

- Parkinson’s Disease Positives (3)

A
  • Long-term efficacy and survival
  • Improved quality of life
  • Improved motor function
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12
Q

Neural Grafting

- Parkinson’s Disease Negatives

A
  • Most patients don’t benefit
  • Ethical and logistical issues using fetal tissue
  • Most grafted cells die (90%)
  • Grafted tissue is not innervated or regulated
  • Disease process may affect graft
  • Side effects (dyskinesia)
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13
Q

Neural Stem Cells

- Location

A

Sub-ventricular zone at the anterior horn of the lateral ventricles

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14
Q

Neural Stem Cells

- Supply

A
  • Olfactory bulb via the rostral migratory stream (RMS)

- Dentate gyrus granule cells in the hippocampus

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15
Q

Neural Stem Cells

  • Location
  • Role
A

Hippocampus

Learning and antidepressant drug action

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16
Q

Neural Stem Cells

- Rodents

A

CNS injury can induce stem cells to produce new neurones in rodents which migrate to the site of injury and differentiate

There is no evidence that such neurones have functional benefit in humans, if they are produced

17
Q

Neural Stem Cells

- Use

A

Not useful for grafting

18
Q

Stem Cell Grafting

- Induced Pluripotent Stem Cells Discovery Steps

A
  1. Cloning experiments by John Gurdon showed that a nucleus of a differentiated cell can be reprogrammed to reverse cell differentiation and produce all cells of the body
  2. Differentiated cells were transfected with transcription factors and formed pluripotent self-renewing cells
19
Q

Stem Cell Grafting

- Pluripotent Stem Cell Differentiation in vitro vs Neural Progenitor Cell (NPC) Cell Populations in vivo

A

Pluripotent stem cell differentiation steps resemble neuralprogenitoy cell (NPC) populations

  1. Pluripotent cells resemble embryonic stem cells
  2. Neuroepithelial cells (NPCs) resemble neural plate cells
  3. Rosette-type neuroepithelial cells (NPCs) resemble neural tube cells
  4. Radial glial-like neural progenitor cells resemble cells in the fetal and adult brain
20
Q

Stem Cell Grafting

- Parkinson’s Disease

A
  • Embryonic stem cells
  • Induced pluripotent stem cells

Triggered to differentiate into dopamine neurone progenitors and are grafted into the patient

21
Q

CNS Neurone Degeneration

A

Distal stump of the axon degenerates following injury

22
Q

CNS Neurone Regeneration In Injured CNS Environment

A

CNS neurones sprout after injury from the proximal stump, but CNS axons cannot regenerate >1mm

CNS neurones cannot regenerate in injured CNS environment

23
Q

Experimental CNS Neurone Regeneration

A

CNS neurones can extend axons experimentally

24
Q

CNS Neurone Regeneration in Injured CNS Environment

- 7 Reasons

A
  • Impaired re-expression of axon growth-associated genes
  • Inhibitory protein NogoA
  • Astrocyte scar
  • Growth inhibitors mechanisms
  • Lack of growth-promoting molecules
  • Lack of growth-facilitating molecules
  • Axon guidance repellents
25
Q

CNS Neurone Regeneration in Injured CNS Environment

- Impaired Re-Expression of Axon Growth-Associated Genes

A

Neurones that survive injury have impaired re-expression of axon growth associated genes

26
Q

CNS Neurone Regeneration in Injured CNS Environment

- NogoA

A

NogoA is a myelin protein that inhibits axon branching and, by retrograde signalling, down regulates the neuronal growth programme

Anti-NogoA antibodies are shown to facilitate axon growth

27
Q

CNS Neurone Regeneration in Injured CNS Environment

- Inhibitory Environment

A

The CNS may be an inhibitory environment for axon growth

  • CNS neurones can extend their axons in vivo peripheral nerve grafts
  • Axons will avoid oligodendrocytes

NAB (37 decks)

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