Stroke is the third most common cause of death in the United States and the leading cause of serious, long-term disability. Recent work in the area of stroke and brain ischemia have a significant inflammatory response (early responses) accompanying necrotic injury. Although later responses may be beneficial in recovery and repair, future studies are attempting to address the timing of inflammation responses. What this article does is discuss roles of specific cells types (leukocytes, endothelium, microglia, the extracellular matrix) as well as the intracellular inflammatory pathways. As well as discussing the mediators produced by inflammatory cells (cytokines, ROS, etc.) and then linking everything together in the process of inflammation following stroke.
This is an overview of inflammation following stroke beginning with brain ischemia which then triggers inflammatory responses in the presence of necrotic cells. This then generates ROS (reactive oxidative species) and produces inflammatory cytokines with neurons which initiate microglial activation that produces more cytokines causing upregulation of adhension molecules in the cerebral vasculature. At the same time chemokines lead to inflammatory cell chemotaxis to the ischemic brain. The adhesion molecules modulate adhesion of circulating leukocytes to the vascular endothelia and infiltration into the brain parenchyma. When in the brain, the activated leukocytes and microglia produce a diverse amount of inflammatory mediators such as matrix metalloproteinases, inducible nitric oxide synthase (generates nitric oxide), cytokes and more ROS. All which leads to brain edema, hemorrhage and eventually cell death.
When future studies are concluded about later responses playing a important role in recovery and repair, we will be able to reduce the risk of stroke and brain ischemia.
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So this is sort of a "chicken or egg" thing...does the inflammation lead to the stroke or TIA, or does the person have a small TIA (maybe unknown) and this leads to the inflammation seen? Is there any way to tease this out?
Something that I noticed in reading this article ('The Inflammatory Response in Stroke')..."MMPS are known to associate with factors involved in angiogenesis such as vascular endothelial growth factor (VEGF)." Interestingly, it is mentioned prior to this statement that matrix metalloproteinases contribute significantly to ischemic brain injury in early activation. Since MMPs later play an important role in plasticity and recovery, by means of VEGF association, it seems that we are again addressed with the issue of timing. I think our question should be: “how could the same protease inhibit oxygen perfusion at one point and then turn around and participate in angiogenesis to increase oxygen shortly after?” To me, this seems like a reperfusion simulation. Would it be possible to research the mechanism by which MMPs participate in blood vessel growth and the return of blood flow so that we could better treat patients in the necessary reperfusion process?
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