CoChat
Sign Up
Cited by 53Neuroinflammation and Neurodegeneration MechanismsAcute Ischemic Stroke ManagementChemokine receptors and signaling

Higher Plasma Fractalkine Is Associated With Better 6-Month Outcome From Ischemic Stroke

Open access
Donohue, Megan M., Cain, Kevin, Zierath, Dannielle, Shibata, Dean, Tanzi, Patricia M., Becker, Kyra J.·2012·Stroke
DOI 10.1161/strokeaha.112.657411PMC PMC3429728
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND AND PURPOSE: Fractalkine (CX3CL1) is a unique chemokine that is constitutively expressed on neurons where it serves as an adhesion molecule for lymphocytes and monocytes. CX3CL1 may also be cleaved from the surface of these cells and enter the circulation to act as a traditional chemokine. CX3CL1 could thus influence the inflammatory response after stroke. We hypothesized that patients with higher plasma CX3CL1 after stroke would have a more robust inflammatory response and experience worse outcome. METHODS: Plasma CX3CL1 concentrations were assessed in 85 patients who were part of a larger study evaluating immune responses after ischemic stroke; CX3CL1 values were available from Day 1 to Day 180 after stroke onset. CX3CL1 was correlated to measures of inflammation and its effect on outcome assessed. RESULTS: At 1 day after stroke, CX3CL1 was lower in patients with severe strokes. At 180 days after stroke, CX3CL1 concentrations were lower in patients with poor outcome. The association of CX3CL1 and outcome at 180 days was independent of initial stroke severity. Plasma CX3CL1 at 180 days was inversely associated with systemic markers of inflammation, including white blood cell counts and high-sensitivity C-reactive protein. CONCLUSIONS: In contrast to our original hypothesis, lower concentrations of CX3CL1 are associated with worse stroke outcome. In light of recent studies suggesting an immunomodulatory and neuroprotective role for CX3CL1 in a variety of neurodegenerative diseases, a therapeutic role for CX3CL1 in stroke recovery should be considered.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1161/strokeaha.112.657411

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Fractalkine upregulation reduces tau pathology and neurodegeneration in an animal model, and elevated plasma fractalkine levels were protective in a stroke population.

    “upregulation of fractalkine, a chemokine that dampens the pro-inflammatory state of microglia and plays a role in adult neurogenesis, has been shown to reduce tau pathology and neurodegeneration in an animal model [57], and elevated plasma fractalkine levels were protective in a stroke population [58].”

    From Evaluation of exploratory fluid biomarkers from a phase 1 senolytic trial in mild Alzheimer's disease (2025) · cites this paper as [58]

    The Results (page not provided) report that plasma fractalkine was lower at 180 days in ischemic-stroke patients with poor outcomes, independently of initial stroke severity. This supports an association between higher levels and better outcomes, but the observational study does not establish that elevated fractalkine was protective. The animal-model claim is attached to a different citation [57]. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 42 · Cited by 53

Research works printed but not linked: 36

  1. [1]Bazan JF Bacon KB Hardiman G Wang W Soo K Rossi D A new class of membrane-bound chemokine with a cx3c motif Nature 1997 385 640 644 9024663
  2. [2]Fong S Jones S Renz ME Chiu HH Ryan AM Presta LG Mucosal addressin cell adhesion molecule-1 (madcam-1). Its binding motif for alpha 4 beta 7 and role in experimental colitis Immunol Res 1997 16 299 311 9379078
  3. [3]Imai T Hieshima K Haskell C Baba M Nagira M Nishimura M Identification and molecular characterization of fractalkine receptor cx3cr1, which mediates both leukocyte migration and adhesion Cell 1997 91 521 530 9390561
  4. [4]Harrison JK Jiang Y Chen S Xia Y Maciejewski D McNamara RK Role for neuronally derived fractalkine in mediating interactions between neurons and cx3cr1-expressing microglia Proc Natl Acad Sci U S A 1998 95 10896 10901 9724801 PMC27992
  5. [5]Ruitenberg MJ Vukovic J Blomster L Hall JM Jung S Filgueira L Cx3cl1/fractalkine regulates branching and migration of monocyte-derived cells in the mouse olfactory epithelium J Neuroimmunol 2008 205 80 85 18951638
  6. [6]Krathwohl MD Kaiser JL Chemokines promote quiescence and survival of human neural progenitor cells Stem Cells 2004 22 109 118 14688397
  7. [8]Bachstetter AD Morganti JM Jernberg J Schlunk A Mitchell SH Brewster KW Fractalkine and cx 3 cr1 regulate hippocampal neurogenesis in adult and aged rats Neurobiol Aging 2011 32 2030 2044 20018408 PMC2889032
  8. [12]Shan S Hong-Min T Yi F Jun-Peng G Yue F Yan-Hong T New evidences for fractalkine/cx3cl1 involved in substantia nigral microglial activation and behavioral changes in a rat model of parkinson’s disease Neurobiol Aging 2011 32 443 458 19368990
  9. [13]Tarozzo G Campanella M Ghiani M Bulfone A Beltramo M Expression of fractalkine and its receptor, cx3cr1, in response to ischaemia-reperfusion brain injury in the rat Eur J Neurosci 2002 15 1663 1668 12059974
  10. [15]Denes A Ferenczi S Halasz J Kornyei Z Kovacs KJ Role of cx3cr1 (fractalkine receptor) in brain damage and inflammation induced by focal cerebral ischemia in mouse J Cereb Blood Flow Metab 2008 28 1707 1721 18575457
  11. [16]Kastenbauer S Koedel U Wick M Kieseier BC Hartung HP Pfister HW Csf and serum levels of soluble fractalkine (cx3cl1) in inflammatory diseases of the nervous system J Neuroimmunol 2003 137 210 217 12667665
  12. [17]Rancan M Bye N Otto VI Trentz O Kossmann T Frentzel S The chemokine fractalkine in patients with severe traumatic brain injury and a mouse model of closed head injury J Cereb Blood Flow Metab 2004 24 1110 1118 15529011
  13. [18]Yajima N Kasama T Isozaki T Odai T Matsunawa M Negishi M Elevated levels of soluble fractalkine in active systemic lupus erythematosus: Potential involvement in neuropsychiatric manifestations Arthritis Rheum 2005 52 1670 1675 15934075
  14. [19]Kasama T Odai T Wakabayashi K Yajima N Miwa Y Chemokines in systemic lupus erythematosus involving the central nervous system Front Biosci 2008 13 2527 2536 17981732
  15. [20]Fassbender K Mossner R Motsch L Kischka U Grau A Hennerici M Circulating selectin- and immunoglobulin-type adhesion molecules in acute ischemic stroke Stroke 1995 26 1361 1364 7543222
  16. [21]Blann A Kumar P Krupinski J McCollum C Beevers DG Lip GY Soluble intercelluar adhesion molecule-1, e-selectin, vascular cell adhesion molecule-1 and von willebrand factor in stroke Blood Coagul Fibrinolysis 1999 10 277 284 10456619
  17. [22]Shyu KG Chang H Lin CC Serum levels of intercellular adhesion molecule-1 and e-selectin in patients with acute ischaemic stroke J Neurol 1997 244 90 93 9120502
  18. [23]Simundic AM Basic V Topic E Demarin V Vrkic N Kunovic B Soluble adhesion molecules in acute ischemic stroke Clin Invest Med 2004 27 86 92 15202827
  19. [24]Lyden P Lu M Jackson C Marler J Kothari R Brott T Ninds tpa stroke trial investigators Underlying structure of the national institutes of health stroke scale: Results of a factor analysis Stroke 1999 30 2347 2354 10548669
  20. [25]van Swieten J Koudstaal P Visser M Schouten H van Gijn J Interobserver agreement for the assessment of handicap in stroke patients Stroke 1988 19 604 607 3363593
  21. [26]Levin HS Boake C Song J McCauley S Contant C Diaz-Marchan P Validity and sensitivity to change of the extended glasgow outcome scale in mild to moderate traumatic brain injury J Neurotrauma 2001 18 575 584 11437080
  22. [27]Sims JR Gharai LR Schaefer PW Vangel M Rosenthal ES Lev MH Abc/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes Neurology 2009 72 2104 2110 19528517 PMC2697964
  23. [28]Zierath D Tanzi P Cain K Shibata D Becker K Plasma {alpha}-melanocyte stimulating hormone predicts outcome in ischemic stroke Stroke 2011 42 3415 3420 21960572 PMC4133930
  24. [29]Tanzi P Cain K Kalil A Zierath D Savos A Gee JM Post-stroke infection: A role for il-1ra? Neurocrit Care 2011 14 244 252 21174170 PMC4096896
  25. [30]Hatori K Nagai A Heisel R Ryu JK Kim SU Fractalkine and fractalkine receptors in human neurons and glial cells J Neurosci Res 2002 69 418 426 12125082
  26. [31]Chapman GA Moores K Harrison D Campbell CA Stewart BR Strijbos PJ Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage J Neurosci 2000 20 RC87 10899174 PMC6772533
  27. [32]Zujovic V Benavides J Vige X Carter C Taupin V Fractalkine modulates tnf-alpha secretion and neurotoxicity induced by microglial activation Glia 2000 29 305 315 10652441
  28. [33]Mizuno T Kawanokuchi J Numata K Suzumura A Production and neuroprotective functions of fractalkine in the central nervous system Brain Res 2003 979 65 70 12850572
  29. [34]Duan RS Yang X Chen ZG Lu MO Morris C Winblad B Decreased fractalkine and increased ip-10 expression in aged brain of app(swe) transgenic mice Neurochem Res 2008 33 1085 1089 18095157
  30. [36]Corona AW Huang Y O’Connor JC Dantzer R Kelley KW Popovich PG Fractalkine receptor (cx3cr1) deficiency sensitizes mice to the behavioral changes induced by lipopolysaccharide J Neuroinflammation 2010 7 93 21167054 PMC3018416
  31. [37]Lauro C Cipriani R Catalano M Trettel F Chece G Brusadin V Adenosine a1 receptors and microglial cells mediate cx3cl1-induced protection of hippocampal neurons against glu-induced death Neuropsychopharmacology 2010 35 1550 1559 20200508 PMC3055460
  32. [38]Cipriani R Villa P Chece G Lauro C Paladini A Micotti E Cx3cl1 is neuroprotective in permanent focal cerebral ischemia in rodents J Neurosci 2011 31 16327 16335 22072684 PMC6633249
  33. [39]Meucci O Fatatis A Simen AA Miller RJ Expression of cx3cr1 chemokine receptors on neurons and their role in neuronal survival Proc Natl Acad Sci U S A 2000 97 8075 8080 10869418 PMC16672
  34. [40]Limatola C Lauro C Catalano M Ciotti MT Bertollini C Di Angelantonio S Chemokine cx3cl1 protects rat hippocampal neurons against glutamate-mediated excitotoxicity J Neuroimmunol 2005 166 19 28 16019082
  35. [41]Deiva K Geeraerts T Salim H Leclerc P Hery C Hugel B Fractalkine reduces n-methyl-d-aspartate-induced calcium flux and apoptosis in human neurons through extracellular signal-regulated kinase activation Eur J Neurosci 2004 20 3222 3232 15610155
  36. [42]Kim TS Lim HK Lee JY Kim DJ Park S Lee C Changes in the levels of plasma soluble fractalkine in patients with mild cognitive impairment and alzheimer’s disease Neurosci Lett 2008 436 196 200 18378084

Authors
Donohue, M. M., Cain, K., Zierath, D., Shibata, D., Tanzi, P. M., & Becker, K. J.
Affiliations
University of Washington (US)
ORCID
Venue
Stroke
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2012-09
Volume
43
Issue
9
Pages
2300-2306
ISSN
  • 0039-2499 (ISSN-L)
  • 1524-4628
DOI
10.1161/strokeaha.112.657411
PMC
PMC3429728
OpenAlex
W2100293635
Cited by
53
References
42
Citations by year
2026: 4 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 7 · 2020: 2 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 6 · 2014: 6 · 2013: 3
FWCI
2.42
Type
journal article
Language
en
Open access
Locations
  • Stroke (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS049197)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Keywords
fractalkine, ischemic stroke, plasma biomarkers, stroke outcome, systemic inflammation, C-reactive protein, white blood cell count, stroke severity, neuroinflammation, neuroprotection
MeSH terms
Aged, C-Reactive Protein, Cerebral Infarction, Brain Ischemia, Female, Humans, Leukocyte Count, Male, Middle Aged, Biomarkers, Treatment Outcome, Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, Stroke, Glasgow Outcome Scale, Chemokine CX3CL1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review