9. Inflammation and Infection In Stroke Flashcards
name the two approved treatments aimed to restore blood flow in stroke
intravenous recombinant tissue plasminogen activator (rtPA)
mechanical thrombectomy (MT)
what is the acute phase response
a group of physiological processes that occur soon after the onset of infection
name an acute phase protein
C-reactive protein (CRP)
when is the inflammatory cascade activated in stroke
immediately after vessel occlusion
what is first released after stagnant blood flow appears
P-selectin
what is the role of P-selectin
attracts circulating leukocytes to the endothelial surface
what is the role of E-selectin
promotes leukocyte adhesion and transmigration through the vessel wall
what activates inflammation in the brain parenchyma
damage-associated molecule patterns (DAMPs)
what produces DAMPs
dying neurons
what do activated microglial cells do
stimulate the inflammasome to release IL-1beta and TNF-alpha
how do these DAMPs and cytokines get access to systemic circulation
via the disrupted BBB or CSF drainage system
what happens when DAMPs and cytokines enter systemic circulation
results in systemic inflammation
what are the two main mechanisms for why there is an increased risk of chest infection after stroke
- Aspiration of food material = by swallowing response
- initial depression of the immune system caused by systemic circulation of novel CNS antigens (which stimulate a t-cell response)
what type of cells have a protective function in stroke
microglia, monocyte derived macrophages
what type of cells have a damaging function in stroke
mast cells and innate lymphocytes
what is the damaging role of mast cells
their activation contributes to BBB breakdown and brain oedema
where do mast cells reside
in the peri vascular space
what is the effect of IL-10 secretion
neuroprotective - it reduces the activity of caspases which have been activated by lipopolysaccharide
this reduces neuronal apoptosis
what is the action of IL-6
proinflammatory = increases vascular risk
what did research of a multi-ethnic cohort reveal in terms of hsCRP to IL-6
when hsCRP is higher than the IL-6 quartile, ischaemic stroke risk was increased
why does inflammation sometimes cause stroke
inflammation is key in destabilising vulnerable plaques with consequent thrombosis and distal thromboembolism
how can microembolic signals be detected
using a transcranial doppler before surgery
what do microembolic signals show
these signals show in vivo measures of plaque inflammation
what was the first cytokine found to act on the brain
interleukin 1
what is the associated actions of IL-1
induced fever
appetite suppression
weight loss
sleep modulation
altered endocrine, neural and immune function
what happens if patients are injected with interleukin-1 receptor antagonist into the occlusion
where is this effect more pronounced
after 1 hour, lesion volume decreased
this effect was more apparent when injected into cortical regions unlike subcortical regions
what is a further action of intravenous IL-1 receptor antagonist
it reduced peripheral markers of inflammation
what may explain the seasonal variance in stroke incidence
environmental factors are at play - e.g. infections precede the stroke.
winter flu may induce stroke occurrance
name 2 types of infections that cause inflammation which can induce stroke
chlamydia pneumoniae
helicobacter pylori
what type of infection is particularly likely to cause stroke
bacterial infection
what % of stroke patients have an infection in the week preceding stroke
10-35%
how can we use this finding of the effect of bacterial infections to reduce stroke risk
administer IL-1 receptor antagonist = this blocks bacterial endotoxin LPS from exacerbating brain damage
IL-1ra blocks the effects of LPS, what exacerbates it?
IL-1 beta
what gives the patient resistance to LPS
having dysfunctional toll like receptor 4 signalling
where are infections in post stroke patients common
in the respiratory tract and the urinary tract
what percentage of deaths within 30 days of admission is due to pneumonia in stroke patients
10%
name 3 predictors of post stroke infection
older age
total anterior circulation infarction
dysphagia
what is pneumonia particularly common in
tube fed patients
what factors make the individual prone to spontaneous infections post stroke
impaired cell-mediated immunity
impaired t-cell activity
what tool can be used to target post stroke infections
vaccinating vulnerable patients
how could SARS-COV2 drive stroke
NLRP3 inflammasomes drive production of cytokines PAMPs and DAMPs. this could induce plaque instability by overdriving the response of macrophages and lymphocytes
how does nitric oxide deficiency arise and what causes it
suppression of nitric oxide synthase = nitric oxide deficiency
results in the loss of vasodilatory effects and promotes the adhesion of platelets and leukocytes to the vessel wall.
how is a mechanical thrombectomy conducted
a catheter is placed through the blood vessels to reach the clot - the catheter is placed through the groin
what is the success rate for mechanical thrombectomy
66% success rate
name a clot busting drug
alteplase
who is eligible to receive clot busting drugs
only those who arrive at the hospital within 90 minutes of stroke symptoms manifesting
what is a limitation of alteplase
it is less able to break down blood clots which are rich in von Willebrand factor
what % of clots are rich in Von Willebrand Factor
50%
who has recently developed a new clot busting drug
the university of manchester
describe the new clot busting drug made by UoM
good success rates in mice who are resistant to current drugs
this drug targets von willebrand factor
the drug also prevented neutrophils from invading brain tissue starved of oxygen preventing inflammation
