BB30044: Stroke (RW)
Stroke:
An interruption in the blood flow to the brain
‘BEFAST’: Earliest symptoms are issues with balance and vision, followed
by a drop in one side of the face, weakening of the arms and legs and loss
of speech.
Ischaemic (clots/ blockages to the brain) – 80% of all strokes are ischaemic
Haemorrhagic (bleeding into the brain)
Transient Ischaemic Attack (temporary blockage to the brain, gives stroke-
like symptoms, increases risk of stroke later in life and increases risk of
developing premature cognitive decline)
Statistics:
Third leading cause of death in UK
Accounts for 11% of deaths in England and Wales
1 in 4 will have stroke by age of 85
25% of strokes in people aged <65
>900,000 people in England who have had a stroke
Leading Cause of Permanent Disability
Impact on Quality of Life
Huge Impact on Socio-Economic System
Risk factors:
Gender: overall risk of stroke across population has a bias towards
women, but this may be because women live longer than men so are at
higher risk of ageing-related diseases.
Family history: e.g. of coronary heart disease
High blood pressure (untreated), TIAs
Ethnic origin: afro-Caribbean population at higher stroke risk
Diabetes (untreated)
Obesity
Heavy alcohol and cocaine use: this is why stroke can be associated with
younger populations. Cocaine use increases blood pressure in
cardiovascular system, increasing stroke risk
Brain vulnerability to blockages:
Brain is a metabolically ‘greedy’ organ. It is very dependent upon blood-
delivered glucose for metabolic activity.
This metabolism produces ATP for the functioning of transporters which
maintain electrophysiological homeostasis in the brain (ion gradients
across membranes)
As an organ, it consumes a large amount of resources (20% of all oxygen,
25% of all glucose) relative to its size (makes up 2-3% of body weight).
Ischaemic vs. Haemorrhagic:
, Ischaemic: brain artery blocked – usually be blood clot
Embolic stroke: clot forms outside the brain
Thrombotic stroke: clot forms within brain artery
Haemorrhagic: brain artery bursts, resulting in bleeding into the brain
Intracerebral: ruptured blood vessel is within the brain, blood enters the
substance of the brain
Subarachnoid: ruptured blood vessel is on the surface of the brain,
blood enters spaces surrounding the brain
Note: infarcts (regions of damage) are often distal to region of blockage,
reflecting the part of brain dependent upon disrupted blood flow.
Cerebral Ischaemia:
Blockage of blood flow to the brain, causing hypoxia and hypoglycaemia
Can be GLOBAL – interruption to entire brain e.g. following cardiac arrest
Can be FOCAL – interruption to particular region following thrombosis or
embolism. Majority are of this type – characterised by an intense foci of
damage (infarct) and region of penumbra (‘shadow’ of damage
surrounding foci).
Therapeutic intervention – penumbra develops hours, days, even weeks
after the ischaemic event so blocking its development may enable brain
function to be retained.
Brain damage occurs particularly in regions with high density of glutamate
receptors. For example, the CA1 region of the hippocampus comprises
neurons that express a large number of glutamate receptors. This means
that these neurons are selectively vulnerable to ischemic damage (lack of
oxygen and glucose for ATP production required for membrane
transporters to prevent glutamate-mediated excitotoxicity). Can block
neuronal loss by applying glutamate receptor antagonist.
Immediate consequences of ischaemic insult:
Rapid depletion of oxygen leads to cessation of oxidative phosphorylation
and mitochondrial respiration. Very limited glycogen is stored in the brain
within glia cells - glucose and glycogen stores are consumed within only 2-
3 min.
Switch to anaeorobic respiration means accumulation of lactate and
increases in CO2 tension. This produces acidosis (brain becomes acidic)
and so inhibition of active transport mechanisms, loss of ionic
homeostasis. Result is oedema (brain swelling).
LEFT PANEL Breakdown of membrane phospholipids by
phospholipases, and release of free fatty acids e.g.
arachidonic acid mobilisation is one of the first
symptoms observed in rodent models of stroke. This
releases free radicals and causes oxidative stress,
leading to neuronal damage.
Loss of calcium homeostasis
Anoxic depolarisation (continual uncontrolled waves
of depolarisation) – excessive release of glutamate into
extracellular space leads to neuronal swelling from ion
and water influx (oedema).
Stroke:
An interruption in the blood flow to the brain
‘BEFAST’: Earliest symptoms are issues with balance and vision, followed
by a drop in one side of the face, weakening of the arms and legs and loss
of speech.
Ischaemic (clots/ blockages to the brain) – 80% of all strokes are ischaemic
Haemorrhagic (bleeding into the brain)
Transient Ischaemic Attack (temporary blockage to the brain, gives stroke-
like symptoms, increases risk of stroke later in life and increases risk of
developing premature cognitive decline)
Statistics:
Third leading cause of death in UK
Accounts for 11% of deaths in England and Wales
1 in 4 will have stroke by age of 85
25% of strokes in people aged <65
>900,000 people in England who have had a stroke
Leading Cause of Permanent Disability
Impact on Quality of Life
Huge Impact on Socio-Economic System
Risk factors:
Gender: overall risk of stroke across population has a bias towards
women, but this may be because women live longer than men so are at
higher risk of ageing-related diseases.
Family history: e.g. of coronary heart disease
High blood pressure (untreated), TIAs
Ethnic origin: afro-Caribbean population at higher stroke risk
Diabetes (untreated)
Obesity
Heavy alcohol and cocaine use: this is why stroke can be associated with
younger populations. Cocaine use increases blood pressure in
cardiovascular system, increasing stroke risk
Brain vulnerability to blockages:
Brain is a metabolically ‘greedy’ organ. It is very dependent upon blood-
delivered glucose for metabolic activity.
This metabolism produces ATP for the functioning of transporters which
maintain electrophysiological homeostasis in the brain (ion gradients
across membranes)
As an organ, it consumes a large amount of resources (20% of all oxygen,
25% of all glucose) relative to its size (makes up 2-3% of body weight).
Ischaemic vs. Haemorrhagic:
, Ischaemic: brain artery blocked – usually be blood clot
Embolic stroke: clot forms outside the brain
Thrombotic stroke: clot forms within brain artery
Haemorrhagic: brain artery bursts, resulting in bleeding into the brain
Intracerebral: ruptured blood vessel is within the brain, blood enters the
substance of the brain
Subarachnoid: ruptured blood vessel is on the surface of the brain,
blood enters spaces surrounding the brain
Note: infarcts (regions of damage) are often distal to region of blockage,
reflecting the part of brain dependent upon disrupted blood flow.
Cerebral Ischaemia:
Blockage of blood flow to the brain, causing hypoxia and hypoglycaemia
Can be GLOBAL – interruption to entire brain e.g. following cardiac arrest
Can be FOCAL – interruption to particular region following thrombosis or
embolism. Majority are of this type – characterised by an intense foci of
damage (infarct) and region of penumbra (‘shadow’ of damage
surrounding foci).
Therapeutic intervention – penumbra develops hours, days, even weeks
after the ischaemic event so blocking its development may enable brain
function to be retained.
Brain damage occurs particularly in regions with high density of glutamate
receptors. For example, the CA1 region of the hippocampus comprises
neurons that express a large number of glutamate receptors. This means
that these neurons are selectively vulnerable to ischemic damage (lack of
oxygen and glucose for ATP production required for membrane
transporters to prevent glutamate-mediated excitotoxicity). Can block
neuronal loss by applying glutamate receptor antagonist.
Immediate consequences of ischaemic insult:
Rapid depletion of oxygen leads to cessation of oxidative phosphorylation
and mitochondrial respiration. Very limited glycogen is stored in the brain
within glia cells - glucose and glycogen stores are consumed within only 2-
3 min.
Switch to anaeorobic respiration means accumulation of lactate and
increases in CO2 tension. This produces acidosis (brain becomes acidic)
and so inhibition of active transport mechanisms, loss of ionic
homeostasis. Result is oedema (brain swelling).
LEFT PANEL Breakdown of membrane phospholipids by
phospholipases, and release of free fatty acids e.g.
arachidonic acid mobilisation is one of the first
symptoms observed in rodent models of stroke. This
releases free radicals and causes oxidative stress,
leading to neuronal damage.
Loss of calcium homeostasis
Anoxic depolarisation (continual uncontrolled waves
of depolarisation) – excessive release of glutamate into
extracellular space leads to neuronal swelling from ion
and water influx (oedema).
