Post-stroke inflammation – target or tool for therapy?

Kate Lykke Lambertsen*, Bente Finsen, Bettina Hjelm Clausen

*Corresponding author for this work

Research output: Contribution to journalReviewResearchpeer-review

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Abstract

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.
Original languageEnglish
JournalActa Neuropathologica
Volume137
Issue number5
Pages (from-to)693-714
ISSN0001-6322
DOIs
Publication statusPublished - May 2019

Keywords

  • Cytokines
  • Drugs
  • Immune therapy
  • Ischemia
  • Neuroprotection

Cite this

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title = "Post-stroke inflammation – target or tool for therapy?",
abstract = "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, throughsoluble 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 andimmunoregulatory functions, their neutralization or augmentation carries a risk of unwanted sideeffects, and clinical translation is therefore challenging. This review summarizes the cell biology ofthe post-stroke inflammatory response and discusses pharmacological interventions targetinginflammation in the acute phase after a stroke that may be used alone or in combination withrecanalization therapies. Development of next-generation immune therapies should ideally aim atselectively neutralizing pathogenic immune signaling, enhancing tissue preservation, promotingneurological recovery and leaving normal function intact.",
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Post-stroke inflammation – target or tool for therapy? / Lambertsen, Kate Lykke; Finsen, Bente; Clausen, Bettina Hjelm.

In: Acta Neuropathologica, Vol. 137, No. 5, 05.2019, p. 693-714.

Research output: Contribution to journalReviewResearchpeer-review

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