Thromboinflammatory challenges in stroke pathophysiology

Semin Immunopathol. 2023 May;45(3):389-410. doi: 10.1007/s00281-023-00994-4. Epub 2023 Jun 5.

Abstract

Despite years of encouraging translational research, ischemic stroke still remains as one of the highest unmet medical needs nowadays, causing a tremendous burden to health care systems worldwide. Following an ischemic insult, a complex signaling pathway emerges leading to highly interconnected thrombotic as well as neuroinflammatory signatures, the so-called thromboinflammatory cascade. Here, we thoroughly review the cell-specific and time-dependent role of different immune cell types, i.e., neutrophils, macrophages, T and B cells, as key thromboinflammatory mediators modulating the neuroinflammatory response upon stroke. Similarly, the relevance of platelets and their tight crosstalk with a variety of immune cells highlights the relevance of this cell-cell interaction during microvascular dysfunction, neovascularization, and cellular adhesion. Ultimately, we provide an up-to-date overview of therapeutic approaches mechanistically targeting thromboinflammation currently under clinical translation, especially focusing on phase I to III clinical trials.

Keywords: Brain ischemia; Neuroinflammation; Platelet; Stroke recovery; Thromboinflammation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Platelets
  • Humans
  • Inflammation
  • Signal Transduction
  • Stroke* / therapy
  • Thrombosis* / etiology