Journal
ACTA NEUROPATHOLOGICA
Volume 137, Issue 5, Pages 693-714Publisher
SPRINGER
DOI: 10.1007/s00401-018-1930-z
Keywords
Cytokines; Ischemia; Immune therapy; Drugs; Neuroprotection
Categories
Funding
- Danish Council for Independent Research, Medical Sciences [DFF-4183-00033]
- Hoerslev Foundation (BHC)
- Lundbeck Foundation [R54-A5539, R173-2014-955, R67-A6383, R126-A11512]
- Novo Nordic Foundation [NNF12OC0002215]
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Inflammation is currently considered a prime target for the development of new stroke therapies. In the acute phase of ischemic stroke, microglia are activated and then circulating immune cells invade the peri-infarct and infarct core. Resident and infiltrating cells together orchestrate the post-stroke inflammatory response, communicating with each other and the ischemic neurons, through soluble and membrane-bound signaling molecules, including cytokines. Inflammation can be both detrimental and beneficial at particular stages after a stroke. While it can contribute to expansion of the infarct, it is also responsible for infarct resolution, and influences remodeling and repair. Several pre-clinical and clinical proof-of-concept studies have suggested the effectiveness of pharmacological interventions that target inflammation post-stroke. Experimental evidence shows that targeting certain inflammatory cytokines, such as tumor necrosis factor, interleukin (IL)-1, IL-6, and IL-10, holds promise. However, as these cytokines possess non-redundant protective and immunoregulatory functions, their neutralization or augmentation carries a risk of unwanted side effects, and clinical translation is, therefore, challenging. This review summarizes the cell biology of the post-stroke inflammatory response and discusses pharmacological interventions targeting inflammation in the acute phase after a stroke that may be used alone or in combination with recanalization therapies. Development of next-generation immune therapies should ideally aim at selectively neutralizing pathogenic immune signaling, enhancing tissue preservation, promoting neurological recovery and leaving normal function intact.
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