Stroke and excitotoxicity Flashcards
What does stroke cause?
Neuronal cell death
What is the root cause of a stroke?
Transient or permanent interruption in cerebral blood supply
What is ischaemia?
A lack of blood supply to a part of the body
Two main causes of stroke?
Ischaemic and haemorrhagic
What causes an ischaemic stroke?
Blocked blood vessels
What causes a hemorrhagic stroke?
Ruptured blood vessels
What are the two types of ischaemic stroke?
Thrombotic or embolic
What is a thrombotic blockage?
A blockage caused by the blood clotting
What is an embolic blockage?
Things like air or fat blocking the blood vessels
Which type of stroke is more fatal?
Haemorrhagic
What are the two types of haemorrhagic stroke?
Intracerebral or subarachnoid
Intracerebral hemorrhagic stroke?
Ruptured blood vessel is inside the brain/provides blood to the centre of the brain
Subarachnoid hemorrhagic stroke?
Ruptured blood vessels are around the outside of the brain
Symptoms of stroke?
Face falling on one side, difficulty raising arms, slurred speech
Time issue with stroke?
Must be treated within 3 hrs
What is necrosis?
cell/tissue death
Two regions of damage post-stroke?
Core and penumbra
What is the core of a stroke?
Where the ischaemia first happened
What is the penumbra in a stroke?
The region around the core
What happens to the core and penumbra regions of a stroke if treatment isnt applied?
The core will grow into the penumbra, damaging more regions of the brain
What is the primary cause of cell death in stroke?
Excitotoxicity
What causes excitotixicity?
Excessive release of glutamate
What happens as a result of excessive glutamate release?
A Ca2+ overload
What allows neurons to have a resting membrane potential of -70mV
The sodium potassium pump
Concentration difference of Na+ in neuronal cells?
Higher outside than inside
Conc grad of K+ in neuronal cells?
Higher inside than outside
What is required for the Na K pump to work?
ATP
Why does ischaemia cause neuronal cell death?
A lack of oxygen/glucose to the neurons
Why does a lack of oxygen/glucose to neurons cause excitotoxicity?
Cant generate ATP to fund NaK pump
What happens if the NaK pump stops working?
The resting potential goes from -70 to +40, all affected neurons will depolarise
What happens if the presunaptic neuron depolarises?
Ca2+ flows in and causes the release of glutamate
What happens if the postsynaptic neuron depolarises?
Positive ions flow in
Consequences of an excessive release of glutamate?
Activate AMPA and KAINATE receptors (both lead to Na+ going into the postsynaptic neuron (more depolarisation))
What happens to NMDA receptors at higher than -40mV?
The magnesium block is removed meaning Na+ can flow through
What does the sodium calcium exchanger do?
Protects the neurons from having too much sodium in them by swapping intracellular Na+ for extracellular Ca2+
Why does having excessive Ca2+ in a neuron cause issues?
It is a signalling molecule that can cause free radicals to form which damage the membrane and cytoskeleton
Which enzymes does Ca2+ activate?
Proteases, lipases, caspaces
What happens as a result of caspase activation?
Cell death
What happens if Ca2+ activates too much of its enzymes?
The lipid bilayer is digested (lipases), as well as anything made of proteins (proteases)
What happens to the neurons in the core of a stroke?
They never repoalrise
What happens to the neurons in the penumbra of a stroke?
They can repolarise
What is difficult about repolarising a penumbra neuron?
The ATPase NaK pump has to work very hard to restore the concentrations of the ions to the correct level for a -70mV membrane potential, and this uses a lot of energy
Which treatment is only for thrombotic ischaemic strokes?
Tissue plasminogen activator (tPA)
What does tPA do?
Breaks down blood clots
Treatment for hemorrhagic stroke?
Surgery to fix the ruptured blood vessel
What are targets for neuroprotective agents for stroke treatment?
AMPA/NMDA receptor blockers, Na+/Ca2+ blockers, enzyme inhibitors
How could neuronal cells be recovered after a stroke?
Stem cells
What are some things that prevent people from having a stroke again?
Antihypertensives
Why are antihypertensives used to prevent stroke?
Reduce high blood pressure
What lifestyle choices can increase risk of stroke?
Obesity, lack of exercise, smoking, alcohol
For which type of stroke are blood thinners prescribed?
Ischaemic
What is a transient ischaemic attack?
Short lived neurological signs similar to those from a stroke
What do the long term stroke symptoms depend on?
The brain region affected
Symptoms if motor cortex is affected?
Skeletal muscle movement affected
Symptoms if wernicke’s area of brain is affected?
Difficulty understanding language/listening
Symptoms if Brocas area of brain is affected?
speech and writing
Symptoms if right motor cortex is comprimised?
Left half of body is affected
What random molecule can cause exitoxicity?
Domoic acid
Why can domoic acid cause excitotoxicity?
It is a glutamate receptor agonist
Where is domoic acid found?
Amnesic shellfish
What produces domoic acid?
Algae
Which glutamate agonists can cause excitotoxicity?
Domoic acid, oxalydiaminopropionic acid, beta-Methylamino-L-alanine
Which foods can cause excitotoxicity?
Shellfish, grass pea, cycad seeds
