Stroke Flashcards
If blood supply to the brain stops, how long will its energy resources last?
5 minutes
What is global ischaemia?
Ischaemia affecting the entire brain or forebrain.
What is focal ischaemia?
Ischaemia involving a single artery such as the middle cerebral artery (MCA)
Why does it take 24-72 hours to see which neurons have survived the ischaemia?
Slow due to apoptosis based damage, rather than necrosis.
Which animal models have been used to study stroke?
Rats
How can a stroke be induced in a rat?
Can introduce a filament or blood clot.
Does white matter or grey matter have a higher blood flow?
Grey matter
How long after a stroke can a T2 scan take place?
24 hours.
What percentage of CNS synapses are glutamatergic?
70%
How many subunits do glutamate receptors have?
4
How are NMDA receptors activated?
Both glutamate and glycine are required to bind to their recognition sites for the NMDA receptor to become activated.
How can ischaemic damage be reduced?
By an NMDA receptor antagonist.
What is the only drug currently licensed for acute stroke?
Actilyse (Alteplase)
A thrombolytic, tissue plasminogen activator.
How can stroke risk be reduced?
By statins and blood pressure lowering therapies such as ACE inhibitors and diuretics.
What are the two types of stroke?
Ischaemic (80%)
Haemorrhagic (20%)
What is a stroke?
Sudden death of brain tissue due to lack of oxygen and glucose delivery.
What happens in an ischaemic stroke?
Blockage in the brain, blood can’t get to cells, cells die.
What happens in a haemorrhagic stroke?
Bleed on the brain, blood accumulates, increased pressure on brain tissue, higher mortality rate.
Which two sources does the brain receive blood from?
Internal carotid arteries
Vertebral arteries.
What do the internal carotid arteries branch into?
Middle cerebral artery
Anterior cerebral artery
What do the right and left vertebral arteries join together to form?
Basilar artery
If one of the main carotid or vertebral arteries are blocked, how can distal smaller arteries receive blood?
Through the circle of Willis.
What is the normal cerebral blood flow?
45-50ml/100g/min
At what CBF does irreversible death occur?
Below 10ml/100g/min
How much blood does the brain consume?
Approx 750ml/min
How is the cerebral perfusion pressure (CPP) measured?
Mean arterial blood pressure - intracranial pressure
What is the effect of carbon dioxide on the cerebral blood flow?
5% carbon dioxide increased CBF by 50%, 7% carbon dioxide increases CBF by 100%
At what pO2 does CBF change?
CBF increases when pO2 drops to about 50 mmHg
Which 5 risk factors account for 80% of stroke?
Hypertension Smoking Abdominal obesity Diet Physical activity
Which symptoms is a middle cerebral artery stroke associated with?
Motor deficits
Sensory impairment
Aphasia
What are the warning signs of a stroke?
Weakness on one side Trouble seeing Trouble walking Trouble speaking Severe headache
How many stroke survivors are dependent on others?
More than half.
What are the most common impacts of a stroke?
Difficulty with general movement
Difficulty moving arms
Alerted sensation
Visual problems
What is a thrombotic stroke?
It is caused by a blood clot in the artery supplying the brain.
What is an embolic stroke?
Blood clot formed elsewhere in the body, travels to brain and blocks blood flow.
What causes a haemorrhagic stroke?
It occurs when a blood vessel in the brain ruptures.
What is an aneurysm?
Ballooning of weakened region of blood vessel.
What is arteriovenous malformation?
Abnormal connection between arteries and veins. Increased risk of bleeding due to increased pressure.
What is the ischaemic core?
Cells which are irreversibly damaged and destined to die.
What is the ischaemic penumbra?
Tissue does not function normally but is still viable and may recover if blood flow is restored or drugs given to support survival.
Why is identification of the ischaemic penumbra important?
Penumbra contains salvageable tissue.
Selection of patients for acute treatment
Acute treatment futile in patients without salvageable tissue.
Patients with penumbra most likely to benefit from clotbuster therapy.
Penumbra is the main target tissue for acute neuroprotection.
Which area of the brain do most ischaemic strokes affect?
Forebrain.
Which kind of imaging can be used to identify the penumbra?
PET imaging.
What happens to the ischaemic penumbra during a stroke?
CBF around 10-15ml/100g/min
Increased OEF, decreased CMRO2
Decreased oxygen availability results in anaerobic glycolysis for ATP generation
CBF and anaerobic clycolysis can maintain ATP for a time but results in increased lactate leading to acidosis.
Protein synthesis inhibition
Peri-infarct depolarisations.
How does brain pH change following a stroke?
Tissue acidosis occurs within the core:
- switch from aerobic glycolysis to anaerobic glycolysis
- generates lactic acid and protons
- acidosis can directly cause damage through activation of acid sensing ion channels (ASIC)
- pH can fall to 6-6.2 within core and penumbra.
Describe the acute phase of brain oedema.
Disturbances in cell volume regulation (intracellular swelling)
Occurs within minutes to hours after stroke onset.
Does not contribute to increases in brain volume.
Describe the delayed phase of brain oedema.
Damage to the blood brain barrier (extracellular oedema)
Movement of macromolecules from vasculature into brain parenchyma.
Describe the pathophysiology of cytotoxic brain oedema.
Ischaemia results in lack of ATP production due to cessation of oxidative metabolism.
ATPase dependent pumps on the cell membrane fail.
The Na+/K+ ATPase is thought to consume 70% of the energy supplied to the brain.
Influx of extracellular ions such as Na+
Na+ influx drives Cl- influx via chloride channels resulting in an increase in osmolarity.
Aquaporin channels allow water influx, increasing cell volume.
Describe the ASIC channel.
Six different subunits
H+ ion gated channels, permeable to Na+/Cl 2+
Activated as pH falls, increased protons
ASIC1a highly expressed in neurons. Inhibition has shown protection in experimental stroke models.
Describe aquaporin channels.
Water transport across membranes occurs passively by diffusion however this is inefficient.
AQPs are specialised water channels.
Small transmemrane proteins that selectively transport water
Fourteen different AQPs identified, 3 in the CNS
AQP4 is most abundant in brain and impolicated in formation of oedema
Facilitate transport of water between the parenchymal space, CSF space and intraventricular space.
Which imagine technique could be used to measure cytotoxic oedema after stroke?
MRI DWI
What are the functions of the blood brain barrier?
- Protects brain from foreign substances in the blood that could injure the brain.
- Protects the brain from hormones and neurotransmitters in the rest of the body.
- Maintains a constant environment for the brain.
What is the neurovascular unit?
Contains neurons and non-neuronal glial cells.
Involved in the control and modulation of regional CBF.
Blood brain barrier regulation.
Injury to any cell will affect function of the entire unit.
What are the consequences of brain oedema?
Brain swelling results in a raised intracranial pressure.
- Typically becomes evident around 1-5 days after stroke.
- As ICP raises Cerebral Perfusion Pressure (CPP) and CBF are reduced
- If CPP drops below the critical autroregulatory limit (around 50-60mmHg) autoregulation fails and CBF is compromised.
- Physical distortion of adjacent brain tissue
- If ICP rises too much then clinical deterioratoin and ultimately death may occur.
What are peri-infarct depolarisations?
Waves of cortical spreading depolarisations that propagate from the ischaemic core through the penumbra.
How does inflammation develop in the ischaemic brain?
Inflammation begins in the intravascular compartment - triggers coagulation cascade - activation of platelets and endothelial cells - fibrin - microvascular occlusions.
Adhesion molecules are upregulated leading to platelet-leukocyte aggregation.
Complement cascade is activated through increased ROS, reduced vasodilation of blood vessels.
MMP release and activation leads to BBB breakdown and facilitates entry of leukocytes across endothelial cell layer.
Mast cells release histamine and proteases and macrophages release cytokines in perivascular space.
What happens once microglia are activated?
They become phagocytes.
Which molecule is vital for post ischaemic angiogenesis?
VEGF.
