Week 10

Question 1

What does trauma include?

Answer 1

Element of Neurotrauma

Brain or spinal cord injury

Question 2

Where does brain and spinal cord injury occur?

Answer 2

Civilian environment

Military environment

Question 3

What is the average intervention time?

Answer 3

12-15 minutes

Question 4

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

Answer 4

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

Question 5

What does a patient who has cervical injury lead to?

Answer 5

Complete tetraplagia

Question 6

Neurotrauma

Answer 6

Injury of young people from ages 16-35

Question 7

Primary injury zone

Answer 7

Irreversible

Die in shallow water and break spine

Question 8

What can primary injury zone be triggered by?

Answer 8

Apoptosis or necrosis

Question 9

What does damage to the spinal cord trigger?

Answer 9

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

Question 10

Secondary injury pathways

Answer 10

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)

Question 11

What is excessive glutamate release defined as?

Answer 11

Excitotoxicity

Question 12

What does reactive vasospasm lead to?

Answer 12

Hypoxia

Question 13

Vessels have increased permeability, what does that lead to?

Answer 13

Influx of substances into the brain

Question 14

What is the consequence of ischemia?

Answer 14

Energy failure

Decreased production of ATP

Question 15

What can oxidative stress lead to?

Answer 15

Expansion of injury zone

Question 16

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

Answer 16

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

Question 17

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

Answer 17

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

Question 18

What is timeline of SCI? (Hours to weeks)

Answer 18

Cellular reactions

Inflammation

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

Apoptosis

Question 19

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

Answer 19

Fibre tract disturbances

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

Question 20

What is the features of cervical?

Answer 20

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

Question 21

What is the features of Thoracic?

Answer 21

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

Question 22

What is spinal cord?

Answer 22

Not homogenous

Question 23

What is the consequence of spinal cord injury?

Answer 23

Paralysed

Can become paraplegic or quadriplegic

Question 24

What does Quadriplegia control?

Answer 24

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

Question 25

What does paraplegia control?

Answer 25

``` Blood pressure Breathing, trunk Sex reflexes Locomotor CPG hip Knee Foot Bladder, bowel ```

Question 26

What is Quadriplegia?

Answer 26

Paralysis of all 4 limbs

Question 27

What is paraplegia?

Answer 27

Paralysis of the legs and lower body | Caused by spinal injury or disease

Question 28

Quadriplegic

Answer 28

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

Question 29

Paraplegic

Answer 29

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

Question 30

What are therapeutic priorities for SCI?

Answer 30

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

Question 31

What are lesions above T5 level associated with?

Answer 31

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

Question 32

What is dysreflexia?

Answer 32

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

Question 33

What can be a trigger of autonomic dysreflexia?

Answer 33

Poo in rectum (sensory stimulation) | Trying to defecate

Question 34

What does Necrosis destroy?

Answer 34

Spinal cord

Question 35

What is NeuN immunostaining used for?

Answer 35

3D reconstruction of compression SCI impact

Question 36

What is Neuraine?

Answer 36

Neuronal antigen which reflects the presence of intact neurons

Question 37

How can you quantify the expansion of injury zone?

Answer 37

High resolution mri

Question 38

Expansion of damage zone

Answer 38

Visible 7-10cm

Question 39

What is secondary injury characterised by?

Answer 39

Inflammation Excitotoxicity Hypoxia collapse of energy resources

Question 40

What are examples of inflammatory compounds?

Answer 40

Anti-integrins | Minocycline

Question 41

Where are 99% of injury done?

Answer 41

Rodents

Question 42

Why does quadrapets recover much more than biceps?

Answer 42

They have locomotion pattern generations

Question 43

How can hind limb score be derived?

Answer 43

Looking at how an animal moved in an open field

Question 44

What drives oxidation in endangered tissue?

Answer 44

Oxidation of lipids and depletion of antioxidants

Question 45

What does 4-HNE reflect?

Answer 45

Oxidation of fatty acids in the tissue

Question 46

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

Answer 46

Brain and spinal cord are full of lipids and phospholipids

Question 47

What is released after injury?

Answer 47

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

Question 48

What does a lipid peroxidatjon have?

Answer 48

Decrease oxidative stress | High T bar signal in rats after compression

Question 49

What is decreased by anti-integrin?

Answer 49

Hydroxyl signal

Question 50

What does MPO stand for?

Answer 50

Myeloperoxidase

Question 51

What is MPO?

Answer 51

Enzyme which characterised a neutrophil

Question 52

What does anti-integrity relieve?

Answer 52

Microglia/macrophage infiltration

Question 53

What happens after treatment with anti-integrity of myelin?

Answer 53

More spared myelin | Some improvement in the rostral and causal areas

Question 54

What is combination of injury?

Answer 54

Loss of sensation | Emergence of neuropathic pain

Question 55

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

Answer 55

A host of diverse pathways activated

Question 56

What is the consequence of injecting EPO?

Answer 56

Induce neuroprotection

Question 57

What does EPO have the potential to improve?

Answer 57

Neurological outcome

Question 58

What does carbamylated EPO do?

Answer 58

Reduce lesion volume