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

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 t...

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Published in:Pharmacology & therapeutics (Oxford) 2019-02, Vol.194, p.73-83
Main Authors: Ouk, Thavarak, Potey, Camille, Maestrini, Ilaria, Petrault, Maud, Mendyk, Anne-Marie, Leys, Didier, Bordet, Regis, Gautier, Sophie
Format: Article
Language:English
Subjects:
Animals
Biomarkers
Cerebral Hemorrhage - chemically induced
Cerebral Hemorrhage - immunology
Fibrinolytic Agents - adverse effects
Hemorrhage
Humans
Life Sciences
Matrix metalloproteinases
Neutrophils
Neutrophils - drug effects
Neutrophils - immunology
Stroke
Stroke - drug therapy
Stroke - immunology
Thrombolysis
Tissue plasminogen activator
Tissue Plasminogen Activator - adverse effects
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Summary: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.
ISSN:0163-7258
1879-016X
0163-7258
DOI:10.1016/j.pharmthera.2018.09.005