Stroke and excitotoxicity

Question 1

What does stroke cause?

Answer 1

Neuronal cell death

Question 2

What is the root cause of a stroke?

Answer 2

Transient or permanent interruption in cerebral blood supply

Question 3

What is ischaemia?

Answer 3

A lack of blood supply to a part of the body

Question 4

Two main causes of stroke?

Answer 4

Ischaemic and haemorrhagic

Question 5

What causes an ischaemic stroke?

Answer 5

Blocked blood vessels

Question 6

What causes a hemorrhagic stroke?

Answer 6

Ruptured blood vessels

Question 7

What are the two types of ischaemic stroke?

Answer 7

Thrombotic or embolic

Question 8

What is a thrombotic blockage?

Answer 8

A blockage caused by the blood clotting

Question 9

What is an embolic blockage?

Answer 9

Things like air or fat blocking the blood vessels

Question 10

Which type of stroke is more fatal?

Answer 10

Haemorrhagic

Question 11

What are the two types of haemorrhagic stroke?

Answer 11

Intracerebral or subarachnoid

Question 12

Intracerebral hemorrhagic stroke?

Answer 12

Ruptured blood vessel is inside the brain/provides blood to the centre of the brain

Question 13

Subarachnoid hemorrhagic stroke?

Answer 13

Ruptured blood vessels are around the outside of the brain

Question 14

Symptoms of stroke?

Answer 14

Face falling on one side, difficulty raising arms, slurred speech

Question 15

Time issue with stroke?

Answer 15

Must be treated within 3 hrs

Question 16

What is necrosis?

Answer 16

cell/tissue death

Question 17

Two regions of damage post-stroke?

Answer 17

Core and penumbra

Question 18

What is the core of a stroke?

Answer 18

Where the ischaemia first happened

Question 19

What is the penumbra in a stroke?

Answer 19

The region around the core

Question 20

What happens to the core and penumbra regions of a stroke if treatment isnt applied?

Answer 20

The core will grow into the penumbra, damaging more regions of the brain

Question 21

What is the primary cause of cell death in stroke?

Answer 21

Excitotoxicity

Question 22

What causes excitotixicity?

Answer 22

Excessive release of glutamate

Question 23

What happens as a result of excessive glutamate release?

Answer 23

A Ca2+ overload

Question 24

What allows neurons to have a resting membrane potential of -70mV

Answer 24

The sodium potassium pump

Question 25

Concentration difference of Na+ in neuronal cells?

Answer 25

Higher outside than inside

Question 26

Conc grad of K+ in neuronal cells?

Answer 26

Higher inside than outside

Question 27

What is required for the Na K pump to work?

Answer 27

ATP

Question 28

Why does ischaemia cause neuronal cell death?

Answer 28

A lack of oxygen/glucose to the neurons

Question 29

Why does a lack of oxygen/glucose to neurons cause excitotoxicity?

Answer 29

Cant generate ATP to fund NaK pump

Question 30

What happens if the NaK pump stops working?

Answer 30

The resting potential goes from -70 to +40, all affected neurons will depolarise

Question 31

What happens if the presunaptic neuron depolarises?

Answer 31

Ca2+ flows in and causes the release of glutamate

Question 32

What happens if the postsynaptic neuron depolarises?

Answer 32

Positive ions flow in

Question 33

Consequences of an excessive release of glutamate?

Answer 33

Activate AMPA and KAINATE receptors (both lead to Na+ going into the postsynaptic neuron (more depolarisation))

Question 34

What happens to NMDA receptors at higher than -40mV?

Answer 34

The magnesium block is removed meaning Na+ can flow through

Question 35

What does the sodium calcium exchanger do?

Answer 35

Protects the neurons from having too much sodium in them by swapping intracellular Na+ for extracellular Ca2+

Question 36

Why does having excessive Ca2+ in a neuron cause issues?

Answer 36

It is a signalling molecule that can cause free radicals to form which damage the membrane and cytoskeleton

Question 37

Which enzymes does Ca2+ activate?

Answer 37

Proteases, lipases, caspaces

Question 38

What happens as a result of caspase activation?

Answer 38

Cell death

Question 39

What happens if Ca2+ activates too much of its enzymes?

Answer 39

The lipid bilayer is digested (lipases), as well as anything made of proteins (proteases)

Question 40

What happens to the neurons in the core of a stroke?

Answer 40

They never repoalrise

Question 41

What happens to the neurons in the penumbra of a stroke?

Answer 41

They can repolarise

Question 42

What is difficult about repolarising a penumbra neuron?

Answer 42

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

Question 43

Which treatment is only for thrombotic ischaemic strokes?

Answer 43

Tissue plasminogen activator (tPA)

Question 44

What does tPA do?

Answer 44

Breaks down blood clots

Question 45

Treatment for hemorrhagic stroke?

Answer 45

Surgery to fix the ruptured blood vessel

Question 46

What are targets for neuroprotective agents for stroke treatment?

Answer 46

AMPA/NMDA receptor blockers, Na+/Ca2+ blockers, enzyme inhibitors

Question 47

How could neuronal cells be recovered after a stroke?

Answer 47

Stem cells

Question 48

What are some things that prevent people from having a stroke again?

Answer 48

Antihypertensives

Question 49

Why are antihypertensives used to prevent stroke?

Answer 49

Reduce high blood pressure

Question 50

What lifestyle choices can increase risk of stroke?

Answer 50

Obesity, lack of exercise, smoking, alcohol

Question 51

For which type of stroke are blood thinners prescribed?

Answer 51

Ischaemic

Question 52

What is a transient ischaemic attack?

Answer 52

Short lived neurological signs similar to those from a stroke

Question 53

What do the long term stroke symptoms depend on?

Answer 53

The brain region affected

Question 54

Symptoms if motor cortex is affected?

Answer 54

Skeletal muscle movement affected

Question 55

Symptoms if wernicke's area of brain is affected?

Answer 55

Difficulty understanding language/listening

Question 56

Symptoms if Brocas area of brain is affected?

Answer 56

speech and writing

Question 57

Symptoms if right motor cortex is comprimised?

Answer 57

Left half of body is affected

Question 58

What random molecule can cause exitoxicity?

Answer 58

Domoic acid

Question 59

Why can domoic acid cause excitotoxicity?

Answer 59

It is a glutamate receptor agonist

Question 60

Where is domoic acid found?

Answer 60

Amnesic shellfish

Question 61

What produces domoic acid?

Answer 61

Algae

Question 62

Which glutamate agonists can cause excitotoxicity?

Answer 62

Domoic acid, oxalydiaminopropionic acid, beta-Methylamino-L-alanine

Question 63

Which foods can cause excitotoxicity?

Answer 63

Shellfish, grass pea, cycad seeds