WEEK 2 STROKE AND CVD Flashcards
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?
- 10%
What is a stroke?
- sudden disruption of the blood supply to a part of the brain
- Loss of blood supply means lower oxygen and thus cerebral ischemia
When there is a loss of blood supply to the brain, we understand that this means less oxygen, however what else does it mean?
- That less glucose will be supplied to the brain which it so crucially needs
What are the two types of stroke classified on?
- What actually causes the brain flow disruption
What are the two major types of stroke?
- Ischaemic stroke
2. Haemorrhagic stroke
What occurs in an ischaemic stroke?
- a blood vessel is occluded by a thrombus
What are the two subtypes of ischaemic stroke?
- Embolic
- thrombotic
What occurs in an embolic ischaemic stroke?
- An embolism in the body (clot) travels to the brain e.g. deep vein thrombosis
What occurs in a thrombotic ischaemic stroke?
- A thrombus grows to block the blood vessel
What occurs in hemorrhagic stroke?
- Rupture of a blood vessel.
What are the two subtypes of hemorrhagic stroke?
- Subarachnoid–> Bleeding in the space around the brain.
- Intracerebral–> Bleeding in the brain tissue itself.
What percentage of strokes does ischemic stroke make up?
85% of strokes.
What percentage of strokes does hemorrhagic stroke makeup?
15% of strokes.
What are the 5 main risk factors for ischemic stroke?
- Hypertension. (70% of strokes)
- Atrial fibrillation (irregular heartbeat)
- Smoking
- Diabetes
- Age
Is the outcome of a stroke worse in males or females?
- Worse in females but males have a higher risk of having one
Why is rapid intervention crucial in the treatment of acute ischaemic stroke?
- 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
What are the 6 steps in the current treatment for ischemic stroke?
- Diagnosis of a stroke type: MRI , CT scan.
- 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)
- High blood pressure treated.
- Anticoagulants, and antiplatelet drugs to thin the blood if ischaemic stroke
- Osmotic agents (and elevation of head) –> if hemorrhagic stroke
- Physiotherapy, speech therapy - as soon as possibly
How many truly effective treatments are there available for ischaemic stroke?
- Only 1!
- rtPA but only if stroke occurred within 4.5 hours
Why can’t rt-PA be given after 4.5 hours of an ischaemic stroke?
- 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)
How does one know if a stroke is occurring?
- 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.
What is an endovascular procedure to correct an ischaemic stroke ?
- Mechanical thrombectomy
In which situations is a mechanical thrombectomy performed?
- 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)
What are the details of how a mechanical thrombectomy occurs?
- 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
What are the downsides of a mechanical thrombectomy?
- 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)
In simple terms, how does hypothermia try and help the downstream effects of a stroke?
- By limiting the brain damage from getting worse q
In what stage of stroke is hypothermia induced and for how long?
- After the ischaemic event occurs and is for 8 hours with a drug that is injected
When referring to the graph about DHC hypothermia, where is the most protection found?
- It is found 2mm away from the bregma position in the brain and is where the HIGHEST protection occurs.
What is the significance f the bregma position?
- It is in the middle of the brain (between the main sutures) and is where the motor cortex is
In the study with the ischaemic stroke hypothermia model, where is the brain damage occurring in the mice?
- Occurring in the cortex
- Gray matter (where the neurons are found)
Which pathways is the hyothermia model in ischaemic stroke thought to decrease?
- 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.
What is an example of the temperature that the body is at for induced hypothermia?
- 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.
Are stem cell therapies using the human’s own stem cells effective in promoting the growth of neurons?
- 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
What are the benefits of using a patients own stem cells for stroke recovery?
- 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
What are the downsides of using patients own stem cells for stroke treatment to encourage growth of new tissue?
- They may have to wait several weeks and the faster the stem cells are administered, the better.
- So the limitation is TIME
What are the cell mechanisms occurring in the time after a stroke which could be weeks after the event?
- Neuroinflammation/oxygen derived free radicals
- We can look at preventing this from occurring in the weeks following a stroke and promoting neural repair
Why are hAECs (Human Amnion Epithelial Cells-placenta) better than induced pluripotent stem cells?
- 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)
Apart from the hAECs, what is the next best stem cell option for stroke?
- Bone marrow derived stem cells
In the mouse experiment, what did hAEC treatment result in ?
- Reduced thionin staining (which is the measure of infarct)
- Improved functional outcomes -
- Limited apoptosis
What is an example of a particular pathway for how hAECs can result in improved stroke outcome?
- they can promote repair mechanisms which result in trophic factors being present (BDNF and NGF-nerve growth factor)
- This increased neuronal survival
What are stem cell derived exosomes?
- Nano-sized extracellular vesicles secreted by stem cells
- contain miRNAs and siRNAs, Lipids and proteins (these regulate reparative functions)
What are the benefits of stem cell derived exosomes compared to the other stem cells?
- Can pass through lungs and BBB
- Can inject higher dose
- ready to inject within minutes
What are the downsides of stem cell derived exosomes?
- they can clump together and get stuck in the microvessels–> issues occur in the lungs –> death
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?
- 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
