Research Paper Volume 12, Issue 1 pp 436—461
Aging exacerbates neutrophil pathogenicity in ischemic stroke
- 1 Department of Neurology, University of Texas Health Science Center, Houston, TX 77030, USA
- 2 Department of Neurology and Center for Neuroepidemiology and Clinical Neurological Research, Yale School of Medicine, New Haven, CT 06520, USA
received: March 10, 2019 ; accepted: December 23, 2019 ; published: January 12, 2020 ;https://doi.org/10.18632/aging.102632
How to Cite
Copyright © 2020 Roy-O’Reilly et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Ischemic stroke is major cause of disability and mortality worldwide, and aging is strong risk factor for poor post-stroke outcome. Neutrophils traffic rapidly to the brain following ischemic stroke, and recent evidence has suggested that aging may alter neutrophil function after tissue injury. In this study, we hypothesize that aging enhances the pro-inflammatory function of neutrophils, directly contributing to the poorer outcomes seen in aging patients. We utilized demographic data and biological specimens from ischemic stroke patients and an experimental mouse model to determine the correlation between age, neutrophil function and stroke outcomes. In ischemic stroke patients, age was associated with increased mortality and morbidity and higher levels of neutrophil-activating cytokines. In mice, aged animals had higher stroke mortality and morbidity, higher levels of neutrophil-activating cytokines and enhanced generation of neutrophil reactive oxygen species compared to young mice. Finally, depletion of neutrophils via a specific monoclonal antibody after ischemic stroke led to long-term benefits in functional outcome in aged male and female animals, with no benefit observed in young. These results demonstrate that aging is associated with augmented neutrophil pathogenicity in ischemic stroke, and that neutrophil-targeted therapies may confer greater benefit in aged subjects.