Targeting Neutrophils in Ischemic Stroke: Translational Insights from Experimental Studies
Top Cited Papers
- 25 March 2015
- journal article
- review article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 35 (6), 888-901
- https://doi.org/10.1038/jcbfm.2015.45
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.Keywords
This publication has 134 references indexed in Scilit:
- The neurovascular unit as a selective barrier to polymorphonuclear granulocyte (PMN) infiltration into the brain after ischemic injuryActa Neuropathologica, 2012
- Neutrophils cascading their way to inflammationTrends in Immunology, 2011
- Significance of marrow‐derived nicotinamide adenine dinucleotide phosphate oxidase in experimental ischemic strokeAnnals of Neurology, 2011
- Extracellular DNA traps promote thrombosisProceedings of the National Academy of Sciences of the United States of America, 2010
- Circulating mitochondrial DAMPs cause inflammatory responses to injuryNature, 2010
- Bone marrow-derived cells are the major source of MMP-9 contributing to blood–brain barrier dysfunction and infarct formation after ischemic stroke in miceBrain Research, 2009
- Neutrophil elastase and neurovascular injury following focal stroke and reperfusionNeurobiology of Disease, 2009
- Inhibition of NADPH Oxidase is Neuroprotective after Ischemia—ReperfusionJournal of Cerebral Blood Flow & Metabolism, 2009
- Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidaseProceedings of the National Academy of Sciences of the United States of America, 2008
- Evidence of the Peripheral Inflammatory Response in Patients With Transient Ischemic AttackJournal of Stroke and Cerebrovascular Diseases, 2007