Much research has been done on the role of inflammation during ischemic stroke, but there have been many contradicting results. Inflammation can have bother damaging and protective effects after stroke depending on what phase it starts. According to the review article, The Inflammatory Response to Stroke, an earlier inflammatory response can increase the damage and a late response is needed for protective and restorative purposes. There are many transcriptional factors that regulate inflammation to work in this way.
Nuclear factor kB is involved in regulating the transcription of inflammatory factors such TNF-alpha, IL-6 and ICAM-1. NF-kB is activated by the phosphorylation of IkB. By blocking IkB phosphorylation, the transcription of inflammatory factors can be blocked. This showed a reduced infarct size in mouse models soon after the stroke but in other cases it showed an increased infarct size. The same discrepancies were seen in other transcription regulatory factors such as Mitogen-activated protein kinase and Activator Protein-1. MAPK plays an important role in transducing stress-related signal cascades. During ischemic stroke it plays a role in activating three different pathways: the stress-activated protein kinases, the p38MAPK’s and extracellular signal-regulated kinases. The activation of these pathways in increased at 30 min and 3 days after ischemia. The inhibition of this pathway can have a protective effect on ischemic injury. Activator Protein-1, on the other hand can promote proliferation of neuronal precursor cells which enhance neurogenesis after ischemia.
These contradicting results go to show that these factors can have damaging and protective effects. The authors of the article state that the effect of these factors depends on the time of release. Early inflammation after stroke can increase the infarct volume and injury where as late inflammation can have protective help with injury repair. More research needs to be done on this switch which could lead to finding the optimal timing of interventions to decrease stroke injury.
I agree with you Rasneet. Inflammation is somewhat "two-faced" (sorry for my lack of a better term) when playing a role in ischemic stroke. Research definitely needs to be done in finding that optimal "window" for reperfusion of the occluded vessel to avoid excessive and detrimental inflammation.
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