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Repair And Regeneration > Week 10 > Flashcards

Week 10 Flashcards

1
Q

What does trauma include?

A

Element of Neurotrauma

Brain or spinal cord injury

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2
Q

Where does brain and spinal cord injury occur?

A

Civilian environment

Military environment

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3
Q

What is the average intervention time?

A

12-15 minutes

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4
Q

What is the drug discovery and transitional path for development of new treatments?

A 
Basic research 
Prototype design or Discovery
Preclinical development 
Clinical development - phase 1/phase2/phase3
FDA filling/ Approval and launch
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5
Q

What does a patient who has cervical injury lead to?

A

Complete tetraplagia

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6
Q

Neurotrauma

A

Injury of young people from ages 16-35

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7
Q

Primary injury zone

A

Irreversible

Die in shallow water and break spine

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8
Q

What can primary injury zone be triggered by?

A

Apoptosis or necrosis

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9
Q

What does damage to the spinal cord trigger?

A 
Loss of cells 
Loss of axons 
Degeneration of axons 
Myelinated fragmented 
Lots of action of glial cells surrounding area of injury
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10
Q

Secondary injury pathways

A

Inflammation
Invasion of neutrophils/macrophages
When spinal cord is damaged - break the BBB
Inflammation -local- driven by microglia
Release of many pro-inflammatory cytokines (IL-6, TNF-A and IL-1B)

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11
Q

What is excessive glutamate release defined as?

A

Excitotoxicity

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12
Q

What does reactive vasospasm lead to?

A

Hypoxia

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13
Q

Vessels have increased permeability, what does that lead to?

A

Influx of substances into the brain

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14
Q

What is the consequence of ischemia?

A

Energy failure

Decreased production of ATP

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15
Q

What can oxidative stress lead to?

A

Expansion of injury zone

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16
Q

What is time line of SCI (seconds to minutes)?

A

Vascular alterations

  1. Hemorhage
  2. Thrombosis
  3. Decreased blood flow
  4. Ischemic necrosis
  5. Edema

Metabolic disturbances

  1. Increased sodium, chloride, potassium
  2. Increase calcium intracellarly
  3. Increase glucose utilisation
  4. Decreased ATP
  5. Acidosis
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17
Q

What is timeline of SCI? (Minutes to hours)?

A

Biochemical alterations

Lipid periodisation

  1. Increase free radicals and fatty acid production
  2. Increase arachidonic acid release
  3. Increase Eicosanoid synthesis

Neurotransmitter accumulation

  1. Increase excitotoxic amino acids, catecholamine
  2. Increase endogenous opioids
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18
Q

What is timeline of SCI? (Hours to weeks)

A

Cellular reactions

Inflammation

  1. Increase macrophages
  2. Increase neutrophils and T cells
  3. Increase reactive astroglia

Apoptosis

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19
Q

What is timeline of SCI? (seems to months)?

A

Fibre tract disturbances

  1. Demyelination
  2. Wallerian degeneration
  3. Apoptosis of oligodendrocytes
  4. Scar formation
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20
Q

What is the features of cervical?

A
  1. Smaller and more mobile vertebrae
  2. Greater diameter
  3. Highly vascularised
  4. Susceptible to hemorrhage
  5. Considerable spontaneous recovery
  6. Injury interrupts sympathetic innervation to major immune organs
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21
Q

What is the features of Thoracic?

A
  1. Larger vertebrae supported by the rib cage
  2. Smaller diameter
  3. Reduced vascular supply and greater pedicure coverage
  4. Less vulnerable to haemorrhage
  5. Minor spontaneous recovery
  6. Injuries below T9 do not interrupt sympathetic innervation to major immune organs
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22
Q

What is spinal cord?

A

Not homogenous

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23
Q

What is the consequence of spinal cord injury?

A

Paralysed

Can become paraplegic or quadriplegic

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24
Q

What does Quadriplegia control?

A

Breathing (C1-4), head, neck (C2)
Heart rate (C4-6), shoulder (C5)
Wrist, elbow (C6-7)
Hand, finger (C7-T1)

25
Q

What does paraplegia control?

A 
Blood pressure
Breathing, trunk
Sex reflexes
Locomotor CPG hip
Knee
Foot 
Bladder, bowel
26
Q

What is Quadriplegia?

A

Paralysis of all 4 limbs

27
Q

What is paraplegia?

A

Paralysis of the legs and lower body

Caused by spinal injury or disease

28
Q

Quadriplegic

A 
Arms/hand function 
Sexual function 
Trunk stability 
Bladder/Bowel/AD
Walking movement 
Normal sensation 
Chronic pain
29
Q

Paraplegic

A 
Sexual function 
Bladder/bowel/AD
Trunk stability 
Walking movement 
Chronic pain 
Normal sensation 
Arm/hand function
30
Q

What are therapeutic priorities for SCI?

A
  1. Intervene early with neuroprotection
  2. Regeneration and restoration of circuitry
  3. Prevent delayed function
  4. Autonomic dysfunction
  5. Dysreflexia
31
Q

What are lesions above T5 level associated with?

A

Sympathetically-driven intense vasoconstriction triggered by peripheral afferent stimulation below injury level

32
Q

What is dysreflexia?

A

Over-activity of the ANS causing abrupt onset of excessively high blood pressure

33
Q

What can be a trigger of autonomic dysreflexia?

A

Poo in rectum (sensory stimulation)

Trying to defecate

34
Q

What does Necrosis destroy?

A

Spinal cord

35
Q

What is NeuN immunostaining used for?

A

3D reconstruction of compression SCI impact

36
Q

What is Neuraine?

A

Neuronal antigen which reflects the presence of intact neurons

37
Q

How can you quantify the expansion of injury zone?

A

High resolution mri

38
Q

Expansion of damage zone

A

Visible 7-10cm

39
Q

What is secondary injury characterised by?

A

Inflammation
Excitotoxicity
Hypoxia collapse of energy resources

40
Q

What are examples of inflammatory compounds?

A

Anti-integrins

Minocycline

41
Q

Where are 99% of injury done?

A

Rodents

42
Q

Why does quadrapets recover much more than biceps?

A

They have locomotion pattern generations

43
Q

How can hind limb score be derived?

A

Looking at how an animal moved in an open field

44
Q

What drives oxidation in endangered tissue?

A

Oxidation of lipids and depletion of antioxidants

45
Q

What does 4-HNE reflect?

A

Oxidation of fatty acids in the tissue

46
Q

Why is there a lot of fatty acids in the tissues?

A

Brain and spinal cord are full of lipids and phospholipids

47
Q

What is released after injury?

A

Pro-inflammatory eicosanoids
(Concentrated in the nervous system - it is an oligo-6 fatty acid)
In the first hour you see a high level of PGF or TXB2

48
Q

What does a lipid peroxidatjon have?

A

Decrease oxidative stress

High T bar signal in rats after compression

49
Q

What is decreased by anti-integrin?

A

Hydroxyl signal

50
Q

What does MPO stand for?

A

Myeloperoxidase

51
Q

What is MPO?

A

Enzyme which characterised a neutrophil

52
Q

What does anti-integrity relieve?

A

Microglia/macrophage infiltration

53
Q

What happens after treatment with anti-integrity of myelin?

A

More spared myelin

Some improvement in the rostral and causal areas

54
Q

What is combination of injury?

A

Loss of sensation

Emergence of neuropathic pain

55
Q

What happens when EPO binds to EPO receptor in the brain?

A

A host of diverse pathways activated

56
Q

What is the consequence of injecting EPO?

A

Induce neuroprotection

57
Q

What does EPO have the potential to improve?

A

Neurological outcome

58
Q

What does carbamylated EPO do?

A

Reduce lesion volume

Repair And Regeneration (16 decks)

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