Targeting Neutrophils in Ischemic Stroke: Translational Insights from Experimental Studies

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 su...

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Bibliographic Details
Published in:Journal of Cerebral Blood Flow & Metabolism 2015-06, Vol.35 (6), p.888-901
Main Authors: Jickling, Glen C, Liu, DaZhi, Ander, Bradley P, Stamova, Boryana, Zhan, Xinhua, Sharp, Frank R
Format: Article
Language:English
Subjects:
Animals
Atherosclerosis - complications
Atherosclerosis - immunology
Brain - immunology
Brain - pathology
Brain Ischemia - complications
Brain Ischemia - immunology
Brain Ischemia - pathology
Brain Ischemia - therapy
Humans
Neutrophils - immunology
Neutrophils - pathology
Review
Stroke - complications
Stroke - immunology
Stroke - pathology
Stroke - therapy
Thrombosis - complications
Thrombosis - immunology
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Summary: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.
ISSN:0271-678X
1559-7016
DOI:10.1038/jcbfm.2015.45