CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke
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ORIGINAL ARTICLE
CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke Meaghan Roy-O’Reilly 1 & Rodney M. Ritzel 2 & Sarah E. Conway 3,4 & Ilene Staff 4 & Gilbert Fortunato 4 & Louise D. McCullough 1,4
Received: 27 October 2016 / Revised: 2 June 2017 / Accepted: 8 June 2017 # Springer Science+Business Media, LLC 2017
Abstract Circulating levels of the pro-inflammatory cytokine C-C motif chemokine 11 (CCL11, also known as eotaxin-1) are increased in several animal models of neuroinflammation, including traumatic brain injury and Alzheimer’s disease. Increased levels of CCL11 have also been linked to decreased neurogenesis in mice. We hypothesized that circulating CCL11 levels would increase following ischemic stroke in mice and humans, and that higher CCL11 levels would correlate with poor long-term recovery in patients. As predicted, circulating levels of CCL11 in both young and aged mice increased significantly 24 h after experimental stroke. However, ischemic stroke patients showed decreased CCL11 levels compared to controls 24 h after stroke. Interestingly, lower post-stroke CCL11 levels were predictive of increased stroke severity and independently predictive of poorer functional outcomes in patients 12 months after ischemic stroke. These results illustrate important differences in the peripheral inflammatory response to ischemic stroke between mice and human patients. In addition, it suggests CCL11 as a candidate
Electronic supplementary material The online version of this article (doi:10.1007/s12975-017-0545-3) contains supplementary material, which is available to authorized users. * Louise D. McCullough [email protected] 1
Department of Neurology, University of Texas Health Science Center, Houston, TX 77030, USA
2
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06032, USA
3
Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA
4
Hartford Hospital, 80 Seymour Street, Hartford, CT 06106, USA
biomarker for the prediction of acute and long-term functional outcomes in ischemic stroke patients. Keywords Stroke . Eotaxin . CCLL1 . Inflammation . Neuroinflammation . Ischemia
Introduction CCL11 (also known as eotaxin-1) is a chemokine that plays a role in a variety of pathologic conditions, including allergy, coronary heart disease, and inflammatory bowel disease [1–3]. Although traditionally thought of as an eosinophil chemokine, CCL11 can be secreted by a variety of cell types, including lymphocytes, monocytes, endothelial cells, and neurons [4, 5]. Levels of circulating CCL11 increase with normal aging in both human serum and plasma, and exogenous delivery of CCL11 was recently shown to decrease neurogenesis in rodents [6, 7]. Circulating levels of CCL11 also increase significantly after traumatic brain injury in mice, suggesting that CCL11 may play a negative role in functional outcome after neurological injury by suppressing neurogenesis [8]. We hypothesized that peripheral CCL11 l
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