Targeting neutrophils in ischemic stroke: Translational insights from experimental studies

Glen C. Jickling, Da Liu, Bradley Ander, Boryana Stamova, Xinhua Zhan, Frank R Sharp

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

Neutrophils have key roles in ischemic brain injury, thrombosis, and atherosclerosis. As such, neutrophils are of great interest as targets to treat and prevent ischemic stroke. After stroke, neutrophils respond rapidly promoting blood-brain barrier disruption, cerebral edema, and brain injury. A surge of neutrophil-derived reactive oxygen species, proteases, and cytokines are released as neutrophils interact with cerebral endothelium. Neutrophils also are linked to the major processes that cause ischemic stroke, thrombosis, and atherosclerosis. Thrombosis is promoted through interactions with platelets, clotting factors, and release of prothrombotic molecules. In atherosclerosis, neutrophils promote plaque formation and rupture by generating oxidized-low density lipoprotein, enhancing monocyte infiltration, and degrading the fibrous cap. In experimental studies targeting neutrophils can improve stroke. However, early human studies have been met with challenges, and suggest that selective targeting of neutrophils may be required. Several properties of neutrophil are beneficial and thus may important to preserve in patients with stroke including antimicrobial, antiinflammatory, and neuroprotective functions.

Original languageEnglish (US)
Pages (from-to)888-901
Number of pages14
JournalJournal of Cerebral Blood Flow and Metabolism
Volume35
Issue number6
DOIs
StatePublished - Jun 1 2015

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Keywords

  • atherosclerosis
  • cerebral ischemia
  • immune system
  • neutrophil
  • stroke
  • thrombus

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Neurology

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