ELM 10.2 Flashcards
Inhibition of IL-1 markedly ______ injury
ihibits
reducing inflammation _____ stroke
reduces
_______ interleukin 1 will reduce inflammation
blocking
we produce a small amount of interleukin-1 when we have ____
a fever
Which of the following cell types are involved in inflammatory responses in the brain?
a. Astrocytes b. Microglia c. Astrocytes and microglia d. Astrocytes, microglia and oligodendrocytes
c
Microglia are classically referred to as the “immune cells of the brain”. However, astrocytes can produce, and respond to pro-inflammatory molecules such as interleukin-1. They also produce another class of cytokine called chemokines. Chemokines upregulate leukocyte adhesion molecules on the endothelium of the brain’s blood vessels. This allows immune system cells to migrate into the CNS.
In animal models of ischaemic stroke, brain damage is worsened if the animals are given:
a. aspirin b. glutamate receptor antagonists c. interleukin-1 d. tissue plasminogen activator
c
IL-1 is a cytokine: a small peptide signalling molecule. It is known as the “master cytokine” and can initiate and regulate inflammatory responses in conditions such as stroke.
Aspirin is used to prevent stroke (through its anti-inflammatory and anti-thrombotic effects). It is detrimental in haemorrhagic stroke due to its “blood thinning” properties. t-PA drugs can be used to treat ischaemic strokes but need to be administered very quickly if they are to be effective. Glutamate receptor antagonists were trialled as stroke treatments, but they were poorly tolerated because glutamate is important is so many brain systems.
In the brain, the cellular targets of interleukin 1 are:
a. endothelial cells b. glial cells c. neurones d. all of the above
d
Interleukin-1 acts on all three cell types but its detrimental actions are primarily mediated through actions on glial and endothelial cells.
The neurotransmitter that is a major mediator of ischaemic brain damage following a stroke is:
a. calcium b. GABA c. glutamate d. glycine
c
Glutamate, the main excitatory neurotransmitter in the CNS, is very important in stroke. It activates several types of receptor including AMPA and NMDA receptors (which are highly calcium permeable). In ischaemic stroke, glutamate release becomes subject to positive feedback leading to an excitotoxic ischaemic cascade.
A suitable drug for reducing the risk of strokes is:
a. a GABA receptor agonist b. a glutamate receptor antagonist c. a tissue plasminogen activator d. aspirin
d
Aspirin can reduce the risk of stroke. Aspirin is an irreversible inhibitor of cyclo-oxygenase, an important enzyme in the synthesis of mediators of inflammation and platelet aggregation. Aggregation of platelets is important in blood clotting and thrombosis, so aspirin can reduce the risk of ischaemic strokes by making it less likely that a thrombus (blood clot) or embolus (detached blood clot) will block an artery. Aspirin therapy, even at low doses, carries a risk because it makes it more difficult for the blood to clot. This risk is only outweighed by the beneficial effects in people who are at high risk of a stroke or who have already had one. The other options could be used to treat a stroke once it has occurred. TPAs are used in this way. Glutamate antagonists were trialled for stroke therapy but have bad side effects. GABAA agonists (or rather, GABAA positive modulator drugs) are sometimes used in acute stroke but there is some controversy surrounding this strategy.
An example of a cytokine is:
a. bradykinin b. β-interferon c. kinesin d. substance P
b
Interferons are cytokinins produced in response to pathogens. They can activate and modulate the immune system.
Substance P is a neuropeptide neurotransmitter involved in pain signalling. Bradykinin is an autocoid (a local hormone) that causes blood vessels to dilate. Kinesin is an ATP-powered motor protein.
A protein that acts as an endogenous pyrogen in the hypothalamus is:
a. interleukin-1 b. leu-enkephalin c. leukotriene-D4 d. prostaglandin E2
a
Interleukin-1 is a cytokine signalling molecule that is produced in high amounts by cells of the immune system during an inflammatory response. One of its other effects is in the thermoregulatory centre of the hypothalamus – the body’s thermostat – where it causes an increase in body temperature (fever). Pyrogen comes from the Greek pyretos (=fever) and means “generator of fever”.
In stroke, the main action of IL-1 is to:
a. cause the release of toxins from glia b. decrease the production of adhesion molecules by the vasculature c. increase the release of growth factors d. promote fever
a
This is thought to be one of the main ways IL-1 causes pathology in stroke. IL-1 does promote fever in response to an infection, but the levels in a stroke are much lower. It also increases the production of growth factors (which may actually be beneficial). However, It increases the production of adhesion molecules.
An endogenous cytokine competitive antagonist is:
a. Pro IL-1 beta b. IL-1Ra c. TNF d. NGF
b
IL-1Ra is interleukin 1 receptor antagonist. It is a naturally occurring competitive antagonist of IL-1 and is currently being explored as a therapeutic for stroke and other conditions that cause brain injury.
