Post-stroke inflammation – target or tool for therapy?

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 poststroke 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.