- Dissolves clot - Found to be effective only shortly after stroke - TPA would make it worse if it is a bleed in the brain, not a clot that causes the stroke

Stroke and brain killers 1 Flashcards by Miayla Marcus

What are brain killers and give examples?

• Brain killers – neurodegenerative diseases (result in death to areas of brain)

Stroke
Brain injury
Multiple sclerosis
Parkinson’s disease
Motor neurone disease
Alzheimer disease
Brain tumours
Epilepsy
CJD (mad cow disease)

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What are common features of brain killer disease?

Neuronal damage/death
Acute and chronic
Age is a risk factor for all of them

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What is a stroke?

Reduced blood flow and oxygen to the brain

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What are some causes of stroke?

 Brain artery blocks
 Brain artery bleeds 
 Poor general circulation 
 Heart failure 
 Drowning 
 Low oxygen at birth 
- limited treatment once stroke has taken place

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What is Ischemia?

The condition of low blood supply

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What is the brain critically dependent on?

A constant blood supply

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What stops large molecules from getting into the brain?

The blood brain barrier

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What are the risk factors for stroke?

Atherosclerosis
Age
Diabetes (doubles the risk)
Ethnic origin (mor common in African-Caribbean people)
Excessive alcohol
Family history of stroke
Heart disease
High blood pressure
High blood cholesterol
Obesity and inactive lifestyle
Smoking
All the same risk factors as a heart attack

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What are symptoms of stroke?

Sudden severe headache with no known cause (for haemorrhagic stroke)
Unexplained dizziness, unsteadiness or sudden falls, especially with any of the other signs
Sudden difficulty speaking or trouble understanding speech
Sudden dimness of loss of vision, particularly in one eye
Sudden weakness or numbness of the face arm or leg on one side of the body
F.A.S.T – facial weakness, arm and leg weakness, speech problems, test these signs

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What is the damage caused by a stroke every minute?

Every minute:
2 million brain cells lost
14 billion connections gone
7.5 miles of ‘wiring’ destroyed

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What is the percentage prevalence of different types of stroke?

50%: athero-thrombo-embolism cerebral arterial supply (clot or blockage)
20%: embolism from heart
25%: intracranial small vessel disease (damage to blood vessel in brain)
5%: rare causes: such as cocaine

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What is an Ischaemic stroke?

Vessel becomes blocked, normally blood clot but sometimes other debris
Most common type of stroke

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What is a Haemorrhagic stroke and what are the different types?

Vessel bursts into the brain (intracranial haemorrhage)
Vessel burst into space around the brain (subarachnoid haemorrhage)
Reduced blood supply

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What does TPA do?

Dissolves clot
Found to be effective only shortly after stroke
TPA would make it worse if it is a bleed in the brain, not a clot that causes the stroke

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What are brain killers believed to be?

Agents in the brain causing damage

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What is used to look at the brain?

CT scans and PET

- PET imaging can show function as well as structure

what is the area of tissue damaged in a stroke called?

an infarct

Talk about the development of ischaemic damage?

Ischaemic core: lowest blood supply where damage initially quite severe
The core of the stroke is called an Umbra
 Cells in immediate area
 Die within minutes- hours
 Beyond rescue
 Core dead tissue
Ischaemic penumbra: area surrounding varied in size where blood supply can be almost normal
 Surrounding regions
 Blood supply compromised but not cut off
 Penumbra Vulnerable tissue
 Cells under ‘threat’ but not dead
 Potential for rescue
 Must start treatment early
Cells in the core dead tissue release toxins which may worsen damage or kill cells in the Penumbra

What are the brain killers?

Neurotransmitters
 Glutamate
Ions
 Calcium, sodium
Free radicals
 Abnormal oxygen molecules - superoxides
 Glutamate and ions turn into this after a stroke

What is the cascade of events you see after a stroke?

Excitotoxicity:
Damaged cells start to release molecules like glutamate
Cause other cells to depolarise and activate
This makes damage worse
Over time see inflammation and apoptosis (a form of cell death)

What is Excitotoxicity?

Main cause of damage in the brain
Glutamate release acts on NMDA and AMPA receptors, they open up channels that allow influx of calcium. Cells get overloaded by calcium. This damages mitochondria, increases release of nitric oxide, lead to protease activation and phospholipase activation. These all lead to free radical formation
Normally glutamate is rapidly taken up by glia, but if there is a lack of energy (ATP) then pumps that usually take up glutamate stop working and glutamate levels carry on to increase due to positive feedback

What has been attempted to combat excitotoxicity?

Attempt to block both release of glutamate and action on it’s MMDA and AMPA receptors and to stop the entry of calcium and calcium overload, and to block increase in nitric oxide:
NMDA and AMPA antagonists and calcium channel blockers

What else is affected in a stroke apart from neurones?

Capillary – surrounded by glia which have end feet onto the blood vessel
Astrocyte important in taking up glutamate
Microglia
Oligodendrocyte

What is reperfusion injury?

Restoration of blood flow to an area of the brain previously rendered ischaemic by a thrombotic blockade of a key artery
Caused by lysis or dislodgement of the clot
Results in inflammation and oxidative stress
Free radicals important in stress

What is a TIA (transient ischaemic attack)?

- Slight occlusion of blood - Mini stroke - Won’t usually cause long lasting damage - Often indicates that another stroke will occur - Multiple TIAs can accumulate and lead to vascular dementia – often associated with small vascular disease

What are some post stroke disabilities and what is the best treatment for them?

- Paralysis/ motor control - Sensory disturbance (pain) - Language problems - Memory impairment - Depression/ anxiety - Best treatments are various therapies

What are some treatments to prevent strokes?

- Aspirin - Statin - Controlling diabetes - Controlling if overweight, alcohol drinking, smoking

What are the different reparative mechanisms of stroke?

- plasticity - neurogenesis - angiogenesis

What is plasticity and how can it be enhanced?

 Often possible for other parts of the brain to take over the functions that were lost due to stroke  Exercise, electrical stimulation, ARBs, light therapy can enhance plasticity  More important in young people

What is neurogenesis?

 In certain regions of the brain new cells can be formed |  Subventricular zone you can get neurogenesis

What is angiogenesis?

 Genesis of new blood vessels  Particularly important in repair of other blood vessels  Subventricular zone you can get angiogenesis

What is the feature of stroke treatment?

- Combination treatment - Strategies to promote recovery • Blocking calcium and glutamate hasn’t proved very successful

When else has excitotoxicity been seen?

after head injuries and in chronic diseases such as Parkinson's and dementia

why has cooling been (unsuccessfully) tried to treat a stroke?

- Brain is very dependent on oxygen because of high metabolism - If metabolism can be reduced (by cooling) then brain would maybe need a less of an oxygen supply (this helps with head injury though)

What have studies in animal models demonstrated in regard to cooling?

* Studies in animal models have demonstrated that cooling to around 32 degrees can produce substantial benefits and be tolerated for quite long periods (> 1 day) * Like with thrombolytic treatment, therapeutic outcomes are best if hypothermia is induced as soon as possible after the ischaemic event. However, neuroprotection still occurs if the treatment is delayed somewhat, provided it is maintained for 1-2 days. This is an important finding because there are often delays in initiating treatment when someone has a stroke

What are cooling mechanisms?

* It’s quite likely that cooling the brain has a diverse range of effects on stroke pathology * In the early stages of a stroke it’s likely that reducing excitotoxicity and decreasing brain oxygen demands plays a major role. It may also help prevent some of the issues with the microcirculation that can occur when an ischaemic area becomes reperfused * In the later stages of a stroke, hypothermia seems to have beneficial effects by reducing apoptosis and reducing inflammation. It may also help reduce the disruption of the blood brain barrier.

What are the limitations to do with cooling?

* It is difficult to move from animal experiments into clinical use in humans * It is much easier to cool a rodent than a 70kg human – in some studies it has been achieved using ice packs or cooling blankets but more precise control can be achieved using a cooling catheter inserted into the femoral vein and threaded up into the vena cava. Another approach is to try and selectively cool the brain, rather than targeting the whole body * A second issue is how to circumvent the body’s homeostatic mechanisms and prevent shivering (which will increase the body temperature). The most common approach is to use opioids as these drugs block thermoregulatory responses * There is a risk of serious complications like pneumonia

What does NICE guidance currently state about cooling?

NICE guidance currently states that it should not be used because of the risk of serious complications and also a lack of good evidence for improved outcomes.