5 - blood supply to the brain and cerebral ischaemia lecture Flashcards
what is the major vessel type in the brain?
capillaries
blood supply to the brain is supplied by what 2 pairs of arteries?
- internal carotid arteries
- vertebral arteries
what arteries are included in the anterior and posterior circulation?
anterior = common carotid artery + internal carotid artery
posterior = subclavian artery + vertebral arteries
what artery runs along the pons and medulla?
basilar artery
describe the anterior cerebral artery
- smaller branch of ICA
- has important branches — anterior communicating, mediate striate artery
what does occlusion of the ACA cause?
paralysis and sensory loss in contralateral leg and perineum
what is the major artery affected in stroke?
middle cerebral artery
describe the MCA
- 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
what are the lateral lenticulostriate arteries?
branches of the MCA that provide supply to basal ganglia
M1 vs M2 vs M3 of middle cerebral artery
- M1 = horizontal segment (gives rise to lateral lenticlostriate arteries which supply basal ganglia)
- M2 = sylvian segment
- M3 = cortical segment
what does occlusion of the MCA cause?
- contralateral paralysis (mostly in lower face and in the ar)
- general somatosensory deficits
- speech deficits (aphasia) if dominant hemisphere affected
describe the basilar artery
- 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
what does occlusion of the basilar artery cause?
coma — followed by death due to respiratory failure (as it supplies brainstem = where CV and resp centres are)
describe the posterior cerebral artery
- curve around midbrain and reach medial surface of cerebral hemisphere
- important branches — cortical branches supply visual cortex, posterior choroidal, posterior communicating
what does occlusion of posterior cerebral artery cause?
blindness
what is the circle of willis? function? limitations?
- 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
laterally, what are the arterial territories (ACA, MCA, PCA)?
medially, what are the arterial territories (ACA, MCA, PCA)?
fill in the gaps with what would be affected by a stroke in each location
what does FAST stand for in ACT FAST?
face, arm, speech, time
describe the acute pathophysiology in an ischaemic stroke
- energy failure (due to drop in blood supply — drop in O2 and ATP)
- anoxic depolarisation of cell membranes, excitotoxicity, oxidative stress, necrosis
- peri-infarct depolarisation, calcium overload, mitochondrial damage (release reactive O2 species)
- inflammation, programmed cell death
- infarcted tissue
what is haemorrhage?
rupture of a blood vessel
describe the intracerebral haemorrhage pathophysiology
what is the penumbra?
vulnerable tissue ‘under threat’ — will turn into core dead tissue if not treated early
describe the core vs penumbra after a stroke
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
what provides close coupling between vessel and neurone and allow blood supply to change very quickly to allow supply to active neurones?
astrocytes
what is the major excitatory neurotransmitter in the brain?
glutamate
describe excitotoxicity
- 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
describe oxidative stress
= 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
describe post-ischaemic inflammation
reperfusion is changes in vasculature which allow what to happen?
allow the activation of inflammatory cells and migration of immune cells into brain tissue
what 2 things does reperfusion cause?
- inflammatory cell activation — releases cytokines which activate different membrane proteases
- free radical formation — cell membrane injury and changes in intracellular processes — cell death
what happens when there is a clot/damage to a vessel?
- tight junctions broken down
- exposure of underlying basement membrane
- vWF released
- binds platelets — bind fibrin, RBCs, neutrophils etc
what is the result of migration of neutrophils and other immune cells into brain tissue?
they release contents (cytokines, proteases, reactive O2 species) which damage neurones
what is the result of thrombo-inflammation?
neuronal death
name some post-stroke complications
- motor impairment
- aphasia
- visual problems
- cognitive problems
- new onset dementia
- anxiety
- language comprehension
- depression
what do damaged neurones release?
DAMPs = damaged associated molecular patterns
what do DAMPs do?
- 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
what is sterile inflammation?
= inflammation in the absence of a pathogen
- no pathogen therefore the released substances cause damage instead of activating neurtophils
what does infiltration of cells and activation of resident cells happen in response to?
damage to basement membrane and BBB
what is Il-1?
- pro-inflammatory cytokine
- acts on hypothalamus to cause fever
- also released by brain in response to injury
Il-1 in stroke treatment?
- 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
what happens in the brain in repair and recovery after a stroke?
> 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
what is tPA?
- tissue plasminogen activator
- catalyses the conversion of plasminogen to plasmin
- given in a hyper-acute setting
- open up vessels and allow recovery
what are problems with tPA?
> 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)
what are some possible treatment targets in the pathophysiology of stroke?
- 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)
stroke is a dynamic phenomenon :
initiates with an ____ insult resulting in a ____ ____ infarct, followed by ______ and _____ events leading to delayed, penumbra cell death
- excitotoxic insult
- necrotic core infarct
- inflammatory and oxidative events
