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CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke

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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 biomarker for the prediction of acute and long-term functional outcomes in ischemic stroke patients.

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Acknowledgements

This work was funded by the National Institutes of Health NS094543 and NS076293 (to LDM), the Hartford Hospital Research Department, and the Russell and Diana Hawkins Family Foundation Discovery Fellowships to the Graduate School at UTHealth (to MAR) and the National Institutes of Health 1F30NS098628 (to MAR).

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Authors and Affiliations

  1. Department of Neurology, University of Texas Health Science Center, Houston, TX, 77030, USA

    Meaghan Roy-O’Reilly & Louise D. McCullough

  2. Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, 06032, USA

    Rodney M. Ritzel

  3. Department of Medicine, Brigham and Women’s Hospital, Boston, MA, 02115, USA

    Sarah E. Conway

  4. Hartford Hospital, 80 Seymour Street, Hartford, CT, 06106, USA

    Sarah E. Conway, Ilene Staff, Gilbert Fortunato & Louise D. McCullough

Authors
  1. Meaghan Roy-O’Reilly
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  2. Rodney M. Ritzel
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  3. Sarah E. Conway
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  4. Ilene Staff
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  5. Gilbert Fortunato
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  6. Louise D. McCullough
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Corresponding author

Correspondence to Louise D. McCullough.

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Ethical Approval

All sample collection performed in studies involving human participants were conducted in accordance with the ethical standards of the Institutional Review Board at Hartford Hospital and the University of Connecticut Health Center and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. All animal procedures were performed in accordance with the NIH guidelines for the care and use of laboratory animals and approved by the Animal Care Committee of the University of Connecticut Health Center.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Funding

This study was funded by the National Institutes of Health NS094543 and NS076293 (to LDM) and the Hartford Hospital Research Department, and the Russell and Diana Hawkins Family Foundation Discovery Fellowships to the Graduate School at UTHealth (to MAR) and the National Institutes of Health 1F30NS098628 (to MAR).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Roy-O’Reilly, M., Ritzel, R.M., Conway, S.E. et al. CCL11 (Eotaxin-1) Levels Predict Long-Term Functional Outcomes in Patients Following Ischemic Stroke. Transl. Stroke Res. 8, 578–584 (2017). https://doi.org/10.1007/s12975-017-0545-3

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  • DOI: https://doi.org/10.1007/s12975-017-0545-3

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