L16 - BBB and SCI Flashcards
Is SCI mainly in young males or females?
Young males
2 Main causes of SCI - and how many %
Trauma - transport related and falls (80%)
Disease (20%)
Difference between complete and incomplete SCI? What are the functional deficits determined by?
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
T/F: Amount of blood correlates with the amount of SC
T
Tissue loss is BIPHASIC - it has two phases:
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
What is responsible for the secondary injury/tissue loss?
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
2 ways to go about dealing with secondary tissue loss
1) Reduce tissue loss - neuroprotection
2) Replace what’s lost - regen, stem cell implants
Neuroprotection - what questions should we ask ourselves?
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?
Timing of grey matter loss is limited to < _ mm either side of injury side where complete loss by _ day/(s)
<4 mm, 1 day
White matter loss occurs over a shorter/longer period of time compared to grey matter?
Longer - 1 week
______ ______ was the standard anti-inflammatory treatment to reduce oedema
Methyl-prednisolone
*HOWEVER these days side effects outweigh benefits so isn’t used anymore
Hyperbaric oxygen therapy
Enhances the body’s natural healing process by inhalation of 100% oxygen in a total body chamber, where atmospheric pressure is increased and controlled.
!Acid-sensing Ion Channel 1A (ASIC1A) - It is present on? Allows _ and _ entry into cells and thought to activate?
Most neurons and glia, Ca2+ and Na+, activate intrinsic apoptotic pathway due to low pH depol mito. membrane
!ASIC1A channel blocker
Psalmotoxin (PcTx1) - large cysteine knot protein (gives it stability to resist cleavage and high temp)
What improves after using psalmotoxin after SCI?
Improved motor function and white matter preservation
Humans can only regen spinal cord up to _ weeks of gestation. Regen is lost when myelination of axons occurs.
8
Nogo-A - what is it? In CNS or PNS myelin?
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).
Can we replace what’s lost using stem cell implants?
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
Electrical stimulation near SCI to maintain bone mass and density
Electrical stimulation near SCI to maintain bone mass and density
What would be a promising therapy?
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
Why have replication studies failed?
- 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)
4 factors in an adequate exp design
1) Randomisation
2) Blinding
3) Sample sizes
Data handling - inclusion/exclusion criteria, how outliers defined, missing data reported
