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BMS3052_ > WEEK 2 STROKE AND CVD > Flashcards

WEEK 2 STROKE AND CVD Flashcards

1
Q

Out of those people that have a stroke and survive (2/3), what is the chance that they will have another stroke that is fatal?

A
  • 10%
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2
Q

What is a stroke?

A
  • sudden disruption of the blood supply to a part of the brain
  • Loss of blood supply means lower oxygen and thus cerebral ischemia
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3
Q

When there is a loss of blood supply to the brain, we understand that this means less oxygen, however what else does it mean?

A
  • That less glucose will be supplied to the brain which it so crucially needs
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4
Q

What are the two types of stroke classified on?

A
  • What actually causes the brain flow disruption
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5
Q

What are the two major types of stroke?

A
  1. Ischaemic stroke
  2. Haemorrhagic stroke
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6
Q

What occurs in an ischaemic stroke?

A
  • a blood vessel is occluded by a thrombus
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7
Q

What are the two subtypes of ischaemic stroke?

A
  • Embolic
  • thrombotic
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8
Q

What occurs in an embolic ischaemic stroke?

A
  • An embolism in the body (clot) travels to the brain e.g. deep vein thrombosis
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9
Q

What occurs in a thrombotic ischaemic stroke?

A
  • A thrombus grows to block the blood vessel
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10
Q

What occurs in hemorrhagic stroke?

A
  • Rupture of a blood vessel.
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11
Q

What are the two subtypes of hemorrhagic stroke?

A
  • Subarachnoid–> Bleeding in the space around the brain.
  • Intracerebral–> Bleeding in the brain tissue itself.
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12
Q

What percentage of strokes does ischemic stroke make up?

A

85% of strokes.

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13
Q

What percentage of strokes does hemorrhagic stroke makeup?

A

15% of strokes.

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14
Q

What are the 5 main risk factors for ischemic stroke?

A
  • Hypertension. (70% of strokes)
  • Atrial fibrillation (irregular heartbeat)
  • Smoking
  • Diabetes
  • Age
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15
Q

Is the outcome of a stroke worse in males or females?

A
  • Worse in females but males have a higher risk of having one
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16
Q

Why is rapid intervention crucial in the treatment of acute ischaemic stroke?

A
  • Because time is crucial for the brain for example for every hour you don’t treat a stroke, you have 120 million neurons lost which leads to 3.6 years of accelerated aging thus taken off life expectancy
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17
Q

What are the 6 steps in the current treatment for ischemic stroke?

A
  1. Diagnosis of a stroke type: MRI , CT scan.
  2. If the stroke is ischemic and occurred [4.5 hours, the clot buster enzyme rt-PA will be injected (but only works in 2-8% of patients)
  3. High blood pressure treated.
  4. Anticoagulants, and antiplatelet drugs to thin the blood if ischaemic stroke
  5. Osmotic agents (and elevation of head) –> if hemorrhagic stroke
  6. Physiotherapy, speech therapy - as soon as possibly
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18
Q

How many truly effective treatments are there available for ischaemic stroke?

A
  • Only 1!
  • rtPA but only if stroke occurred within 4.5 hours
  • Only approved drug therapy
  • Dcrease neurological damage (stop furthur damage)
  • Given within 4.5 h of stroke
  • > 4.5 h ­ risk of haemorrhage
  • Only used in 5-10% of patients
  • Most commonly limited by delayed hospital presentation time

*Can be given 9 h post-stroke*

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19
Q

Why can’t rt-PA be given after 4.5 hours of an ischaemic stroke?

A
  • As this is a ‘clot buster’ drug, it will lead to thinning of the blood and after 4.5 hours it can lead to increased risk of hemorrhage. (you DON’T want further bleeding)

Note: Only 10% of the patient recieve rt-PA and 3% recieve benefit.

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20
Q

How does one know if a stroke is occurring?

A
  • Usually based on the person they are with
  • droopy side to the face
  • Arms are tingly
  • Could occur at night though so difficult to tell when it occurred.
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21
Q

What is an endovascular procedure to correct an ischaemic stroke ?

A
  • Mechanical thrombectomy
22
Q

In which situations is a mechanical thrombectomy performed?

A
  • Patients with an occlusion of the large cerebral artery
  • must be within 24 hours of a stroke
  • Patient receives rt-PA first (if before 4.5 hours)
23
Q

What are the details of how a mechanical thrombectomy occurs?

A
  • Stent inserted through femoral artery to correct occlusion in cerebral artery –> it collects the clot and keeps the artery open so the body can remove the clot
  • Only performed in patients with occlusion of large cerebral artery
24
Q

What are the downsides of a mechanical thrombectomy?

A
  • Patient MUST receive the rt-PA first so very SMALL subset of patients (could be clinical trials though where you don’t have to receive it)
  • Performed in patients with an occlusion in the LARGE cerebral artery…so not for smaller vessels
  • You need ADVANCED surgery equipment for this so less access and only in built up hospitals (not rural)
25
Q

In simple terms, how does hypothermia try and help the downstream effects of a stroke?

A
  • By limiting the brain damage from getting worse q
26
Q

In what stage of stroke is hypothermia induced and for how long?

A
  • After the ischaemic event occurs and is for 8 hours with a drug that is injected
27
Q

When referring to the graph about DHC hypothermia, where is the most protection found?

A
  • It is found 2mm away from the bregma position in the brain and is where the HIGHEST protection occurs.
28
Q

What is the significance f the bregma position?

A
  • It is in the middle of the brain (between the main sutures) and is where the motor cortex is
29
Q

In the study with the ischaemic stroke hypothermia model, where is the brain damage occurring in the mice?

A
  • Occurring in the cortex
  • Gray matter (where the neurons are found)
30
Q

Which pathways is the hyothermia model in ischaemic stroke thought to decrease?

A
  • Ischaemia leading to TXA2 expression which leads to platelet aggregation and vasoconstriction. This then leads to vessel OCCLUSION
  • decrease the path with ischaemia leading to hypoxia. This then results in the reactive oxygen species such as OH-, H2O2 and O2- from building up. These then lead to DNA not being produced from decreased signalling and thus cell death
31
Q

What is an example of the temperature that the body is at for induced hypothermia?

A
  • A study done by Hong et al. 2014 noted that the mean temp was 34.4 degrees celcius as there was decreased cerebral edema and hemorrhagic transformation.
  • Preclinical Studies showed delayed neuronal damage -> Less Brain Damage/Improved Outcomes
  • Clinical studies showed mixed results
32
Q

Are stem cell therapies using the human’s own stem cells effective in promoting the growth of neurons?

A
  • NO
  • This is because you can’t inject 120 million neurons into the brain
  • The issue is that a person suffering a stroke loses SO many neurons by the minute that is is difficult to replace such high numbers
33
Q

What are the benefits of using a patients own stem cells for stroke recovery?

A
  • These cells are not replacing the dead neural tissue, but release approx, 30 chemicals which trigger the growth of new brain tissue in damaged area
34
Q

What are the downsides of using patients own stem cells for stroke treatment to encourage growth of new tissue?

A
  • They may have to wait several weeks and the faster the stem cells are administered, the better.
  • So the limitation is TIME
35
Q

What are the cell mechanisms occurring in the time after a stroke which could be weeks after the event?

A
  • Neuroinflammation/oxygen derived free radicals
  • We can look at preventing this from occurring in the weeks following a stroke and promoting neural repair
36
Q

Why are hAECs (Human Amnion Epithelial Cells-placenta) better than induced pluripotent stem cells?

A
  • Becuase they also have the pluripotent properties BUT are readily available
  • Have immunomodulary properties
  • NO invasive extraction procedures
  • LOW immunogenicity
  • LACK tumorigenicity (whereas the iSCs can form tumours)
  • Differentiate into functional neural tissue
37
Q

Apart from the hAECs, what is the next best stem cell option for stroke?

A
  • Bone marrow derived stem cells
38
Q

In the mouse experiment, what did hAEC treatment result in ?

A
  • Reduced thionin staining (which is the measure of infarct)
  • Improved functional outcomes -
  • Limited apoptosis
39
Q

What is an example of a particular pathway for how hAECs can result in improved stroke outcome?

A
  • they can promote repair mechanisms which result in trophic factors being present (BDNF and NGF-nerve growth factor)
  • This increased neuronal survival
40
Q

What are stem cell derived exosomes?

A
  • Nano-sized extracellular vesicles secreted by stem cells
  • contain miRNAs and siRNAs, Lipids and proteins (these regulate reparative functions)
41
Q

What are the benefits of stem cell derived exosomes compared to the other stem cells?

A
  • Can pass through lungs and BBB
  • Can inject higher dose
  • ready to inject within minutes
42
Q

What are the downsides of stem cell derived exosomes?

A
  • they can clump together and get stuck in the microvessels–> issues occur in the lungs –> death
43
Q

Why is it thought that there is an increase in stroke presentation in young people who have mild/no symptoms with COVID-19 and no CVD risk factors?

A
  • Bc COVID-19 inserts via the ACE2 receptor in epithelial cells which are EVERYWHERE in the body and surround important vessels
  • Thought that this also leads to increased levels of complement –> thus more inflammation and more leukocytes thus ROS and stroke
  • Also because the young people are MORE resistant to respiratory distress from COVID than the elderly
44
Q

Stroke Statistics

A

• ~ 40,000 strokes occur in Australia, hence a stroke occurs every
13-14 minutes
• Stroke is the Australia’s third leading cause of death
• 50% of strokes occur in people 45-75 years old (<45:5%)
• Women are more likely to die after stroke than men
• More women die from stroke than from breast cancer
• In terms of suffering and cost, stroke exceeds all other diseases
• Stroke costs Australians $5 billion each year

45
Q

Outcome of stroke

A
46
Q

Time is Critical

A
47
Q

Tenecteplase

A

• Fibrinolytic drug with higher fibrin specificity and longer halflife than t-PA (alteplase)
• Already has regulatory approval to treat ST-segment–
elevation myocardial infarction

48
Q

Cell Death Mechanisms Following Stroke

A
49
Q

Stem Cell Therapy for Stroke

A
50
Q

Potential Mechanisms by which hAECs May Improve Stroke Outcome

A

BMS3052_ (12 decks)

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