L16 - BBB and SCI

Question 1

Is SCI mainly in young males or females?

Answer 1

Young males

Question 2

2 Main causes of SCI - and how many %

Answer 2

Trauma - transport related and falls (80%)

Disease (20%)

Question 3

Difference between complete and incomplete SCI? What are the functional deficits determined by?

Answer 3

Incomplete injury = function not completely lost, complete = complete loss of sensory and motor function below the level of injury

Determined by spinal level and size of lesion

Question 4

T/F: Amount of blood correlates with the amount of SC

Answer 4

T

Question 5

Tissue loss is BIPHASIC - it has two phases:

Answer 5

Primary damage - occurs at time of injury

Secondary damage - over hours to days after injury

*We could possibly develop treatments to prevent the secondary phase of the injury

Question 6

What is responsible for the secondary injury/tissue loss?

Answer 6

1) Hypoxia
2) Ischaemia
3) Acidosis - due to loss of ATP as it leads to loss of acid pumps
4) Apoptosis - due to loss of ATP

Others include odema, inflammation, NT accumulation, free radicals, vascular changes, electrolyte shifts

Question 7

2 ways to go about dealing with secondary tissue loss

Answer 7

1) Reduce tissue loss - neuroprotection

2) Replace what’s lost - regen, stem cell implants

Question 8

Neuroprotection - what questions should we ask ourselves?

Answer 8

1) Which tissue is at risk? (Grey/white matter)
2) Treatment window for intervention
3) Mechanisms of tissue loss - possible targets for intervention
4) Can we identify effective treatments
5) Can treatments reach target tissue?

Question 9

Timing of grey matter loss is limited to < _ mm either side of injury side where complete loss by _ day/(s)

Answer 9

<4 mm, 1 day

Question 10

White matter loss occurs over a shorter/longer period of time compared to grey matter?

Answer 10

Longer - 1 week

Question 11

______ ______ was the standard anti-inflammatory treatment to reduce oedema

Answer 11

Methyl-prednisolone

*HOWEVER these days side effects outweigh benefits so isn’t used anymore

Question 12

Hyperbaric oxygen therapy

Answer 12

Enhances the body’s natural healing process by inhalation of 100% oxygen in a total body chamber, where atmospheric pressure is increased and controlled.

Question 13

!Acid-sensing Ion Channel 1A (ASIC1A) - It is present on? Allows _ and _ entry into cells and thought to activate?

Answer 13

Most neurons and glia, Ca2+ and Na+, activate intrinsic apoptotic pathway due to low pH depol mito. membrane

Question 14

!ASIC1A channel blocker

Answer 14

Psalmotoxin (PcTx1) - large cysteine knot protein (gives it stability to resist cleavage and high temp)

Question 15

What improves after using psalmotoxin after SCI?

Answer 15

Improved motor function and white matter preservation

Question 16

Humans can only regen spinal cord up to _ weeks of gestation. Regen is lost when myelination of axons occurs.

Answer 16

8

Question 17

Nogo-A - what is it? In CNS or PNS myelin?

Answer 17

Inhibitory to neurite extension - stops axons from extending so they NO GO any further. Membrane spanning protein present on CNS myelin (oligo) but not PNS (Schwann).

Question 18

Can we replace what’s lost using stem cell implants?

Answer 18

Rationale:
Stem cells diff into neurons and glia forming bridging neural pathway across lesion, restoring function

Lesion site

• Often a cystic cavity where there is no physical supports for growing axons and glia
• Any protein favours glial cell diff
• Will new neurons make appropriate connections? (e.g. makes connection with pain pathways leading to pain instead of motor pathway)

Target site
Received little attention in research and vacant synapses replaced by local sprouts - hence reinervated fibres will not find a target site to synapse onto

Question 19

Electrical stimulation near SCI to maintain bone mass and density

Answer 19

Electrical stimulation near SCI to maintain bone mass and density

Question 20

What would be a promising therapy?

Answer 20

1) Works in several animal models
2) Provides robust improvement in structural and functional outcomes
3) Works in different types of SCI
4) Wide therapeutic window
5) Safety issues addressed (Side effects, toxicity)
6) Study is clinically relevant and able to be replicated in an indep lab

Question 21

Why have replication studies failed?

Answer 21

• Exp model diff
• Animal strains and sources
• Diff outcome measures
• Data over-intepretaiton
• Exclusion criteria not described
• Therapy does not work
• Heterogeneity of CNS injury (no two injuries are alike)

Question 22

4 factors in an adequate exp design

Answer 22

1) Randomisation
2) Blinding
3) Sample sizes
Data handling - inclusion/exclusion criteria, how outliers defined, missing data reported