Targeting neutrophils in ischemic stroke: translational insights from experimental studies.
Jickling Glen C,Liu DaZhi,Ander Bradley P,Stamova Boryana,Zhan Xinhua,Sharp Frank R
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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.
10.1038/jcbfm.2015.45
Dynamic increase in neutrophil levels predicts parenchymal hemorrhage and function outcome of ischemic stroke with r-tPA thrombolysis.
Ying AnNa,Cheng YaNi,Lin YanYan,Yu JunRu,Wu XiaoYun,Lin YuanShao
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
BACKGROUND:The higher level of neutrophil on admission has been reported to predict worse 3-month outcomes in ischemic stroke patients. Our study was to explore the dynamic changes of neutrophil and lymphocyte after r-tPA thrombolysis of ischemic stroke and the relationship with parenchymal hemorrhage (PH) and 3-month function outcome. METHODS:A total of 208 acute ischemic stroke (AIS) patients with intravenous thrombolysis were included and then received 3-month follow-up in the present study. Blood samples for neutrophil and lymphocyte counts were obtained on admission, at 24 h and at 7 days after r-tPA infusion. The associations of increase in neutrophil, lymphocyte, and neutrophil to lymphocyte ratio (NLR) with PH or 3-month poor outcome were examined by logistic regression. RESULTS:Increasing trends in the neutrophil and NLR were observed in AIS patients after r-tPA treatment. Increased level of neutrophil at 24 h after r-tPA infusion but not that on admission was associated with PH (OR = 2.86, P = 0.029) and 3-month poorer functional outcomes (OR = 2.67, P = 0.009). Moreover, patients were divided into four groups according to the percent change in neutrophil within 24 h following r-tPA treatment, and we found that there was a trend of incremental OR when compared higher increase group with lower ones. CONCLUSIONS:Dynamic increase in neutrophil and NLR after stroke may predict PH and 3-month poor outcome in AIS patients receiving r-tPA treatment. Therefore, neutrophil and NLR may serve as activity markers for PH and 3-month poor prognosis in AIS patients with intravenous thrombolysis.
10.1007/s10072-020-04324-6