Neutrophils in tPA-induced hemorrhagic transformations: Main culprit, accomplice or innocent bystander?

Pharmacol Ther. 2019 Feb:194:73-83. doi: 10.1016/j.pharmthera.2018.09.005. Epub 2018 Sep 18.

Abstract

The risk of intracerebral hemorrhage still greatly limits the use of tPA in stroke patients. Research is ongoing in order to identify the pathophysiological mechanisms at play, detect predictive biomarkers and discover new pharmacological targets to develop preventive or curative treatments. Going through experimental and clinical studies, this review focuses on the role of neutrophils as key predictive biomarkers for thrombolysis-induced hemorrhages and as pharmacological targets to limit their occurrence. To date, there are no established pharmacological modulators of neutrophils for ischemic stroke and its hemorrhagic complications. Several strategies are under evaluation, including lipid-lowering drugs, free radical scavengers, or minocycline, as well as non-pharmacological interventions such as physical exercise.

Keywords: Hemorrhage; Matrix metalloproteinases; Neutrophils; Stroke; Thrombolysis; Tissue plasminogen activator.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers
  • Cerebral Hemorrhage / chemically induced*
  • Cerebral Hemorrhage / immunology
  • Fibrinolytic Agents / adverse effects*
  • Humans
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Stroke / drug therapy
  • Stroke / immunology*
  • Tissue Plasminogen Activator / adverse effects*

Substances

  • Biomarkers
  • Fibrinolytic Agents
  • Tissue Plasminogen Activator