Cerebral Ischaemia and stroke

Question 1

describe the brain blood supply

Answer 1

two pairs of arteries supply blood to the brain : vertebral arteries (back) and carotid arteries (front) to form the ring of arteries - circle of willis

Question 2

which part of the brain does basilar artery supplies

Answer 2

both spinal cord and brain stem

Question 3

which part of the brain does anterior cerebral artery supplies

Answer 3

medial surface of frontal and parietal lobes

Question 4

which part of the brain does middle cerebral artery supplies

Answer 4

supplies most of the lateral surface of the brain as well as deep structures, such as the basal ganglia and the internal capsule.

Question 5

which part of the brain does posterior cerebral artery supplies

Answer 5

supply the medial surfaces of the occipital (medial wall) and temporal (inferior) lobes as well as the thalamus deep in the forebrain.

Question 6

what does stroke leads to

Answer 6

hemiplegia (paralysis on one side), balance problems, loss of sensations, loss of visual field, language

Question 7

what are the two types of stroke

Answer 7

ischemic and haemorrhagic

Question 8

what are the two types of ischemic stroke

Answer 8

focal ischemia which is confined to a specific region and global ischemia which encompasses the whole brain tissue which is normally caused by cardiac arrest

Question 9

what does focal brain ischemia degree of damage depends on

Answer 9

the extent and duration of occlusion and blood supply from other vessels

Question 10

what causes focal brain ischemia

Answer 10

thrombosis forming a platelet plug and embolism which is a blood clot

Question 11

what is the core in ischemia

Answer 11

the part of tissue that undergoes irreversible damage

Question 12

what is the infarct in ischemia

Answer 12

dead tissues, made from neuron and glial cells suffered from necrotic cell death

Question 13

what is the penumbra in ischemia

Answer 13

area around the dead tissue, not severe enough to cause irreversible damage as collateral arteries supply it with oxygen and glucose

Question 14

What do doctors target therapeutic interventions for ischemia?

Answer 14

target penumbra to preserve tissue from cell death

Question 15

what might cause transient ischaemic attack

Answer 15

high blood pressure, cigarette, heart disease, diabetes

Question 16

what are the two types of haemorrhagic stroke

Answer 16

intracerebral and subarachnoid

Question 17

what is the difference between intracerebral and subarachnoid ischaemia

Answer 17

intracerebral burst inside the brain and leaks into surrounding brain tissue while subarachnoid bleeds between the brain and tissue covering the brain known as subarachnoid space

Question 18

what causes intracerebral and subarachnoid ischaemia

Answer 18

intracerebral is caused by aneurysm (sac-like malformation protruding from vessel wall) and subarachnoid is caused by high blood pressure and aging blood vessels

Question 19

what may subarachnoid further cause

Answer 19

lack of blood, plus compression by the blood leaked out into the tissue
§ forming a solid clot, which also causes secondary inflammation and toxicity

Question 20

what happens when stroke occurred in anterior cerebral artery

Answer 20

• Paralysis of contralateral leg, arm, face
• Disturbance of intellect, executive function and judgement; diminished motivation (abulia)
• Loss of appropriate social behaviour

Question 21

what happens when stroke occurred in middle cerebral artery

Answer 21

• “Classic stroke”: it is the most common site of occlusion.
• Contralateral hemiplegia (i.e. paralysis of one side of the body): arm > leg
• Contralateral sensory deficits
• Hemianopia (i.e. blindness over half the field of vision)
• Aphasia (i.e. impairment of language)

Question 22

what happens when stroke occurred in posterior cerebral artery

Answer 22

Visual deficits
• homonymous hemianopia (i.e. visual field loss on the left or right side of the vertical midline).
• visual agnosia (i.e. a condition in which a person can see but cannot recognize or interpret visual information).

Question 23

which neurons are vulnerable to global ischaemia

Answer 23

• The pyramidal cells of the area CA1 of the hippocampus
  * The pyramidal neurons of the neocortex (layers 3, 5 and 6)
  * The Purkinje cells of the cerebellum
  * The neurons in the striatum

Question 24

Why does the brain require energy ?

Answer 24

to maintain transmembrane ion gradients and to restore them after each action potential

Question 25

why do we need continuous glucose supply

Answer 25

brain cannot store, synthesize or utilize any other source of energy

Question 26

what happens to to reduced glucose delivery to brain

Answer 26

individuals sugar levels drop and individual appears disorientated, slurred speech or impaired motor function

Question 27

what happen when there is a reduction supply of oxygen

Answer 27

anoxia - completely starved of oxygen and ischaemia

Question 28

how do cells die

Answer 28

necrosis (passive) in ischaemic core and apoptosis delayed death in penumbra

Question 29

Describe the necrosis mechanism

Answer 29

1. Ischaemia causes the fall of ATP levels below the levels needed for the Na+-K+-ATPase to maintain ion gradients.
2. Depolarisation causes opening of Ca2+channels.
3. Increased intracellular Ca2+causes glutamate release from synaptic vesicles and extracellularly.
4. Activation of glutamate receptors - NMDA and AMPA allows influx of calcium in the postsynaptic neuron.
5. Excessive calcium accumulation in mitochondria causes dysfunction.
6. Damaged mitochondria produce free oxygen radicals which damage cell structures. Free radicals are generated also by the inflammatory process.
7. Calcium activates a number of enzymes (lipases, proteases) that contribute to the breakdown of the cell components.

Question 30

what is the difference between extrinsic and intrinsic apoptosis

Answer 30

extrinsic is initiated by binding of a death ligand to cell surface receptor while intrinsic started by stress within the cell

Question 31

Similarity between two apoptosis pathway

Answer 31

both requires activation of a sequence of signals, including caspases which induce release of further protein eg. cytochrome c

Question 32

what changes does apoptotic cell undergo

Answer 32

cell shrinkage, chromatin condensation, breakdown of nucleus, cleavage of DNA and blebbing of plasma memrbane and fragmentation of cell into small vesicles

Question 33

how are dead cells engulfed by microglia

Answer 33

• lipid phosphatidylserine on the inner leaflet surface of the plasma membrane
  * redistributed during apoptosis to the extracellular surface, and acts as a “eat me” signal for microglia

Question 34

Treatment for stroke

Answer 34

thrombolytic agent -tPA to dissolve the clot and restore blood flow but only small fraction of patients are eligible, remove clot surgically, preventions

Question 35

Explain key differences between focal and global ischemic stroke

Answer 35

• Focal ischemia occurs when a blood clot or other material (embolus) has occluded a cerebral vessel
  
  • Global brain ischemia occurs when blood flow to the whole brain is halted or drastically reduced. This is commonly caused by cardiac arrest
  • Focal brain ischemia reduces blood flow to a specific brain region, causing cell death. It can be caused by either a platelet plug that forms in the vessel itself (thrombosis), or by a blood clot or other material (such as a fat globule or an air bubble) originated elsewhere (embolism).
  • The part of the tissue that undergoes irreversible damage during an ischemic stroke is termed the ischemic core.
  • The area around it, termed penumbra (“almost shadow” in Latin) still suffers a reduction in blood flow but not severe enough to cause irreversible damage, thanks to sufficient flow from surrounding vessels (“collateral flow”) to keep it alive for some time