5 - blood supply to the brain and cerebral ischaemia lecture

Question 1

what is the major vessel type in the brain?

Answer 1

capillaries

Question 2

blood supply to the brain is supplied by what 2 pairs of arteries?

Answer 2

• internal carotid arteries
• vertebral arteries

Question 3

what arteries are included in the anterior and posterior circulation?

Answer 3

anterior = common carotid artery + internal carotid artery

posterior = subclavian artery + vertebral arteries

Question 4

what artery runs along the pons and medulla?

Answer 4

basilar artery

Question 5

describe the anterior cerebral artery

Answer 5

• smaller branch of ICA
• has important branches — anterior communicating, mediate striate artery

Question 6

what does occlusion of the ACA cause?

Answer 6

paralysis and sensory loss in contralateral leg and perineum

Question 7

what is the major artery affected in stroke?

Answer 7

middle cerebral artery

Question 8

describe the MCA

Answer 8

• larger branch of ICA
• has numerous branches
• passes through the lateral sulcus and travels along lateral surface of frontal and parietal lobes
• most common site of stroke
• divided into M1, M2 and M3

Question 9

what are the lateral lenticulostriate arteries?

Answer 9

branches of the MCA that provide supply to basal ganglia

Question 10

M1 vs M2 vs M3 of middle cerebral artery

Answer 10

• M1 = horizontal segment (gives rise to lateral lenticlostriate arteries which supply basal ganglia)
• M2 = sylvian segment
• M3 = cortical segment

Question 11

what does occlusion of the MCA cause?

Answer 11

• contralateral paralysis (mostly in lower face and in the ar)
• general somatosensory deficits
• speech deficits (aphasia) if dominant hemisphere affected

Question 12

describe the basilar artery

Answer 12

• runs forward in midline on ventral surface of pons
• numerous branches — anterior inferior cerebellar, pontine, superior cerebellar
• divides at rostral end of midbrain - posterior cerebral arteries

Question 13

what does occlusion of the basilar artery cause?

Answer 13

coma — followed by death due to respiratory failure (as it supplies brainstem = where CV and resp centres are)

Question 14

describe the posterior cerebral artery

Answer 14

• curve around midbrain and reach medial surface of cerebral hemisphere
• important branches — cortical branches supply visual cortex, posterior choroidal, posterior communicating

Question 15

what does occlusion of posterior cerebral artery cause?

Answer 15

blindness

Question 16

what is the circle of willis? function? limitations?

Answer 16

• ring of arteries at base of brain — forms an anastomoses
• provides a safety mechanism — if one artery gets blocked the circle will still provide the brain with blood
• however actual significance of this is dependent on size of communicating arteries = highly variable between individuals in elderly population, anastomoses are not sufficient dye to narrowing of large vessels and communicating arteries because of vascular disease

Question 17

laterally, what are the arterial territories (ACA, MCA, PCA)?

Answer 17

Question 18

medially, what are the arterial territories (ACA, MCA, PCA)?

Answer 18

Question 19

fill in the gaps with what would be affected by a stroke in each location

Answer 19

Question 20

what does FAST stand for in ACT FAST?

Answer 20

face, arm, speech, time

Question 21

describe the acute pathophysiology in an ischaemic stroke

Answer 21

1. energy failure (due to drop in blood supply — drop in O2 and ATP)
2. anoxic depolarisation of cell membranes, excitotoxicity, oxidative stress, necrosis
3. peri-infarct depolarisation, calcium overload, mitochondrial damage (release reactive O2 species)
4. inflammation, programmed cell death
5. infarcted tissue

Question 22

what is haemorrhage?

Answer 22

rupture of a blood vessel

Question 23

describe the intracerebral haemorrhage pathophysiology

Answer 23

Question 24

what is the penumbra?

Answer 24

vulnerable tissue ‘under threat’ — will turn into core dead tissue if not treated early

Question 25

describe the core vs penumbra after a stroke

Answer 25

core - cells in immediate area - die within minutes-hours - beyond rescue penumbra - surrounding regions - blood supply compromised but not cut off - cells under ‘threat’ but not dead - potential for rescue - must start treatment early

Question 26

what provides close coupling between vessel and neurone and allow blood supply to change very quickly to allow supply to active neurones?

Answer 26

astrocytes

Question 27

what is the major excitatory neurotransmitter in the brain?

Answer 27

glutamate

Question 28

describe excitotoxicity

Answer 28

- drop in ATP — failure of membrane pumps - glutamate remains in synaptic clefts - cell remains polarised - failure if AMPA and NMDA receptors - excessive levels of calcium in cell - free radical formation - cell death

Question 29

describe oxidative stress

Answer 29

= overproduction of reactive O2 species > drives inflammation - reduction in ATP - mitochondria membranes collapse - reactive oxygen species (H2O2) released - acted upon by free radials such as superoxide, causing them to release hydroxide radicals - these are extremely toxic - leads to changes within the cell —> leads to oxidation of proteins and lipids —> eventually CELL DEATH

Question 30

describe post-ischaemic inflammation

Answer 30

Question 31

reperfusion is changes in vasculature which allow what to happen?

Answer 31

allow the activation of inflammatory cells and migration of immune cells into brain tissue

Question 32

what 2 things does reperfusion cause?

Answer 32

- inflammatory cell activation — releases cytokines which activate different membrane proteases - free radical formation — cell membrane injury and changes in intracellular processes — cell death

Question 33

what happens when there is a clot/damage to a vessel?

Answer 33

- tight junctions broken down - exposure of underlying basement membrane - vWF released - binds platelets — bind fibrin, RBCs, neutrophils etc

Question 34

what is the result of migration of neutrophils and other immune cells into brain tissue?

Answer 34

they release contents (cytokines, proteases, reactive O2 species) which damage neurones

Question 35

what is the result of thrombo-inflammation?

Answer 35

neuronal death

Question 36

name some post-stroke complications

Answer 36

- motor impairment - aphasia - visual problems - cognitive problems - new onset dementia - anxiety - language comprehension - depression

Question 37

what do damaged neurones release?

Answer 37

DAMPs = damaged associated molecular patterns

Question 38

what do DAMPs do?

Answer 38

- they are recognised by brain resident microglia and infiltrating monocytes via pathogen recognition receptors (activate microglia and infiltrating cells) - upregulation of receptors on cell surface and release of cytokines/chemokines, ROS, MMPs etc

Question 39

what is sterile inflammation?

Answer 39

= inflammation in the absence of a pathogen - no pathogen therefore the released substances cause damage instead of activating neurtophils

Question 40

what does infiltration of cells and activation of resident cells happen in response to?

Answer 40

damage to basement membrane and BBB

Question 41

what is Il-1?

Answer 41

- pro-inflammatory cytokine - acts on hypothalamus to cause fever - also released by brain in response to injury

Question 42

Il-1 in stroke treatment?

Answer 42

- il-1 receptor antagonist (IL-1Ra) = anakinra - time of first dose within 6 hours - in phase 3 of clinical trials - safe and effective for ischaemic stroke - being trialled in subarachnoid haemorrhage

Question 43

what happens in the brain in repair and recovery after a stroke?

Answer 43

> the brain can produce new cells — neurogenesis and angiogenesis > brain areas can take over functions from damaged area — plasticity > inflammation may be important — stem cells release inflammatory substances and glial cells secrete growth factors

Question 44

what is tPA?

Answer 44

- tissue plasminogen activator - catalyses the conversion of plasminogen to plasmin - given in a hyper-acute setting - open up vessels and allow recovery

Question 45

what are problems with tPA?

Answer 45

> currently only a small proportion (12%) of patients treatment - needs to be given early and in a controlled setting - stroke services need to be optimal for this to happen > increased risk of haemorrhage > incomplete re-canalisation and high (27%) re-occlusion rate > reperfusion itself can be detrimental (results in inflammation and oxidative stress) > new treatments still required (not thrombectomy as this needs specialist centres and highly trained specialists)

Question 46

what are some possible treatment targets in the pathophysiology of stroke?

Answer 46

- free radical scavengers/antioxidants - nootropic/stimulator — stimulate GFs - growth factors to stimulate neurogenesis, synaptogenesis, axogenesis - antiapoptotic agents - anti inflammatory agents (prevent cytokine release, microglia and leukocyte activation) - calcium antagonists (prevent calcium overload from failure of NMDA receptors)

Question 47

stroke is a dynamic phenomenon : initiates with an ____ insult resulting in a ____ ____ infarct, followed by ______ and _____ events leading to delayed, penumbra cell death

Answer 47

- excitotoxic insult - necrotic core infarct - inflammatory and oxidative events