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Published in: Thrombosis Journal 1/2017

Open Access 01-12-2017 | Research

The CD31 molecule: a possible neuroprotective agent in acute ischemic stroke?

Authors: Tobias Boeckh-Behrens, Justus Kleine, Johannes Kaesmacher, Claus Zimmer, Lucas Schirmer, Sophie Simon, Holger Poppert

Published in: Thrombosis Journal | Issue 1/2017

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Abstract

Background

The transmembrane receptor molecule CD31 is known to have immunomodulatory functions, suggesting a possible neuroprotective effect in the context of acute ischemic stroke by restricting an over-activation of secondary immunological processes. This study examines the density of CD31+ cells in mechanically extracted thrombi of stroke patients with the aim to test whether the occurrence of CD31+ cells was associated with a beneficial clinical outcome in those patients.

Methods

Thrombi of 122 consecutive patients with large anterior circulation stroke were collected during intracranial mechanical recanalization. Out of these, 86 immunostained specimens of adequate quality could be analysed. The density of CD31+ cells was quantified and compared with clinical outcome data of the affected patients.

Results

The density of CD31+ cells was positively related to early patient improvement (ΔNIHSS, r = 0.283, p = 0,012) with an even clearer relationship after exclusion of patients who died in the early hospital phase (r = 0.371, p = 0.001). This finding stayed stable also in the multivariate analysis after corrrection for other outcome-influencing factors (p = 0.049).

Conclusion

This study shows a stable relation between CD31+ cells and early clinical improvement of patients with acute ischemic stroke. This finding is in line with recent reports showing immunomodulatory and potential neuroprotective effects of CD31, suggesting that CD31 may be a promising neuroprotective agent in stroke patients.
Literature
1.
go back to reference De Meyer SF, Denorme F, Langhauser F, Geuss E, Fluri F, Kleinschnitz C. Thromboinflammation in stroke brain damage. Stroke. 2016;47(4):1165–72.CrossRefPubMed De Meyer SF, Denorme F, Langhauser F, Geuss E, Fluri F, Kleinschnitz C. Thromboinflammation in stroke brain damage. Stroke. 2016;47(4):1165–72.CrossRefPubMed
2.
go back to reference Chamorro A, Meisel A, Planas AM, Urra X, van de Beek D, Veltkamp R. The immunology of acute stroke. Nat Rev Neurol. 2012;8(7):401–10.CrossRefPubMed Chamorro A, Meisel A, Planas AM, Urra X, van de Beek D, Veltkamp R. The immunology of acute stroke. Nat Rev Neurol. 2012;8(7):401–10.CrossRefPubMed
3.
go back to reference Boeckh-Behrens T, Schubert M, Forschler A, Prothmann S, Kreiser K, Zimmer C, Riegger J, Bauer J, Neff F, Kehl V, et al. The impact of histological clot composition in embolic stroke. Clin Neuroradiol. 2016;26(2):189–97.CrossRefPubMed Boeckh-Behrens T, Schubert M, Forschler A, Prothmann S, Kreiser K, Zimmer C, Riegger J, Bauer J, Neff F, Kehl V, et al. The impact of histological clot composition in embolic stroke. Clin Neuroradiol. 2016;26(2):189–97.CrossRefPubMed
4.
go back to reference Huber T, Kleine JF, Kaesmacher J, Bette S, Poppert H, Zimmer C, Boeckh-Behrens T. Blood leukocytes as prognostic parameter in stroke thrombectomy. Cerebrovasc Dis. 2016;42(1–2):32–40.CrossRefPubMed Huber T, Kleine JF, Kaesmacher J, Bette S, Poppert H, Zimmer C, Boeckh-Behrens T. Blood leukocytes as prognostic parameter in stroke thrombectomy. Cerebrovasc Dis. 2016;42(1–2):32–40.CrossRefPubMed
5.
go back to reference Schuhmann MK, Gunreben I, Kleinschnitz C, Kraft P. Immunohistochemical analysis of cerebral thrombi retrieved by mechanical thrombectomy from patients with acute ischemic stroke. Int J Mol Sci. 2016;17(3):298.CrossRefPubMedPubMedCentral Schuhmann MK, Gunreben I, Kleinschnitz C, Kraft P. Immunohistochemical analysis of cerebral thrombi retrieved by mechanical thrombectomy from patients with acute ischemic stroke. Int J Mol Sci. 2016;17(3):298.CrossRefPubMedPubMedCentral
6.
go back to reference Dargazanli C, Rigau V, Eker O, Riquelme Bareiro C, Machi P, Gascou G, Arquizan C, Ayrignac X, Mourand I, Corlobe A, et al. High CD3+ cells in intracranial thrombi represent a biomarker of atherothrombotic stroke. PLoS One. 2016;11(5):e0154945.CrossRefPubMedPubMedCentral Dargazanli C, Rigau V, Eker O, Riquelme Bareiro C, Machi P, Gascou G, Arquizan C, Ayrignac X, Mourand I, Corlobe A, et al. High CD3+ cells in intracranial thrombi represent a biomarker of atherothrombotic stroke. PLoS One. 2016;11(5):e0154945.CrossRefPubMedPubMedCentral
7.
go back to reference Marelli-Berg FM, Clement M, Mauro C, Caligiuri G. An immunologist‘s guide to CD31 function in T-cells. J Cell Sci. 2013;126(Pt 11):2343–52.CrossRefPubMed Marelli-Berg FM, Clement M, Mauro C, Caligiuri G. An immunologist‘s guide to CD31 function in T-cells. J Cell Sci. 2013;126(Pt 11):2343–52.CrossRefPubMed
8.
go back to reference Flego D, Severino A, Trotta F, Previtero M, Ucci S, Zara C, Pedicino D, Massaro G, Biasucci LM, Liuzzo G, et al. Altered CD31 expression and activity in helper T cells of acute coronary syndrome patients. Basic Res Cardiol. 2014;109(6):448.CrossRefPubMed Flego D, Severino A, Trotta F, Previtero M, Ucci S, Zara C, Pedicino D, Massaro G, Biasucci LM, Liuzzo G, et al. Altered CD31 expression and activity in helper T cells of acute coronary syndrome patients. Basic Res Cardiol. 2014;109(6):448.CrossRefPubMed
9.
go back to reference Caligiuri G, Rossignol P, Julia P, Groyer E, Mouradian D, Urbain D, Misra N, Ollivier V, Sapoval M, Boutouyrie P, et al. Reduced immunoregulatory CD31+ T cells in patients with atherosclerotic abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol. 2006;26(3):618–23.CrossRefPubMed Caligiuri G, Rossignol P, Julia P, Groyer E, Mouradian D, Urbain D, Misra N, Ollivier V, Sapoval M, Boutouyrie P, et al. Reduced immunoregulatory CD31+ T cells in patients with atherosclerotic abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol. 2006;26(3):618–23.CrossRefPubMed
10.
go back to reference Boeckh-Behrens T, Kleine JF, Zimmer C, Neff F, Scheipl F, Pelisek J, Schirmer L, Nguyen K, Karatas D, Poppert H. Thrombus Histology Suggests Cardioembolic Cause in Cryptogenic Stroke. Stroke. 2016;47(7):1864–71. Boeckh-Behrens T, Kleine JF, Zimmer C, Neff F, Scheipl F, Pelisek J, Schirmer L, Nguyen K, Karatas D, Poppert H. Thrombus Histology Suggests Cardioembolic Cause in Cryptogenic Stroke. Stroke. 2016;47(7):1864–71.
11.
go back to reference Adams Jr HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh 3rd EE. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35–41.CrossRefPubMed Adams Jr HP, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh 3rd EE. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35–41.CrossRefPubMed
12.
go back to reference Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B, Barr J, Dillon W, Warach S, Broderick J, Tilley B, et al. Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke. 2003;34(8):e109–137.CrossRefPubMed Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B, Barr J, Dillon W, Warach S, Broderick J, Tilley B, et al. Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke. 2003;34(8):e109–137.CrossRefPubMed
13.
go back to reference Kerr DM, Fulton RL, Lees KR, Collaborators V. Seven-day NIHSS is a sensitive outcome measure for exploratory clinical trials in acute stroke: evidence from the Virtual International Stroke Trials Archive. Stroke. 2012;43(5):1401–3.CrossRefPubMed Kerr DM, Fulton RL, Lees KR, Collaborators V. Seven-day NIHSS is a sensitive outcome measure for exploratory clinical trials in acute stroke: evidence from the Virtual International Stroke Trials Archive. Stroke. 2012;43(5):1401–3.CrossRefPubMed
14.
go back to reference Biswas P, Canosa S, Schoenfeld D, Schoenfeld J, Li P, Cheas LC, Zhang J, Cordova A, Sumpio B, Madri JA. PECAM-1 affects GSK-3beta-mediated beta-catenin phosphorylation and degradation. Am J Pathol. 2006;169(1):314–24.CrossRefPubMedPubMedCentral Biswas P, Canosa S, Schoenfeld D, Schoenfeld J, Li P, Cheas LC, Zhang J, Cordova A, Sumpio B, Madri JA. PECAM-1 affects GSK-3beta-mediated beta-catenin phosphorylation and degradation. Am J Pathol. 2006;169(1):314–24.CrossRefPubMedPubMedCentral
15.
go back to reference Graesser D, Solowiej A, Bruckner M, Osterweil E, Juedes A, Davis S, Ruddle NH, Engelhardt B, Madri JA. Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1-deficient mice. J Clin Invest. 2002;109(3):383–92.CrossRefPubMedPubMedCentral Graesser D, Solowiej A, Bruckner M, Osterweil E, Juedes A, Davis S, Ruddle NH, Engelhardt B, Madri JA. Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1-deficient mice. J Clin Invest. 2002;109(3):383–92.CrossRefPubMedPubMedCentral
16.
go back to reference Newton-Nash DK, Newman PJ. A new role for platelet-endothelial cell adhesion molecule-1 (CD31): inhibition of TCR-mediated signal transduction. J Immunol. 1999;163(2):682–8.PubMed Newton-Nash DK, Newman PJ. A new role for platelet-endothelial cell adhesion molecule-1 (CD31): inhibition of TCR-mediated signal transduction. J Immunol. 1999;163(2):682–8.PubMed
17.
go back to reference Brown GC, Neher JJ. Microglial phagocytosis of live neurons. Nat Rev Neurosci. 2014;15(4):209–16.CrossRefPubMed Brown GC, Neher JJ. Microglial phagocytosis of live neurons. Nat Rev Neurosci. 2014;15(4):209–16.CrossRefPubMed
18.
go back to reference Kleine JF, Boeckh-Behrens T, Prothmann S, Zimmer C, Liebig T. Discrepancy between early neurological course and mid-term outcome in older stroke patients after mechanical thrombectomy. J Neurointerv Surg. 2016;8(7):671–6.CrossRefPubMed Kleine JF, Boeckh-Behrens T, Prothmann S, Zimmer C, Liebig T. Discrepancy between early neurological course and mid-term outcome in older stroke patients after mechanical thrombectomy. J Neurointerv Surg. 2016;8(7):671–6.CrossRefPubMed
19.
go back to reference Fornasa G, Groyer E, Clement M, Dimitrov J, Compain C, Gaston AT, Varthaman A, Khallou-Laschet J, Newman DK, Graff-Dubois S, et al. TCR stimulation drives cleavage and shedding of the ITIM receptor CD31. J Immunol. 2010;184(10):5485–92.CrossRefPubMedPubMedCentral Fornasa G, Groyer E, Clement M, Dimitrov J, Compain C, Gaston AT, Varthaman A, Khallou-Laschet J, Newman DK, Graff-Dubois S, et al. TCR stimulation drives cleavage and shedding of the ITIM receptor CD31. J Immunol. 2010;184(10):5485–92.CrossRefPubMedPubMedCentral
20.
go back to reference Fornasa G, Clement M, Groyer E, Gaston AT, Khallou-Laschet J, Morvan M, Guedj K, Kaveri SV, Tedgui A, Michel JB, et al. A CD31-derived peptide prevents angiotensin II-induced atherosclerosis progression and aneurysm formation. Cardiovasc Res. 2012;94(1):30–7.CrossRefPubMedPubMedCentral Fornasa G, Clement M, Groyer E, Gaston AT, Khallou-Laschet J, Morvan M, Guedj K, Kaveri SV, Tedgui A, Michel JB, et al. A CD31-derived peptide prevents angiotensin II-induced atherosclerosis progression and aneurysm formation. Cardiovasc Res. 2012;94(1):30–7.CrossRefPubMedPubMedCentral
Metadata
Title
The CD31 molecule: a possible neuroprotective agent in acute ischemic stroke?
Authors
Tobias Boeckh-Behrens
Justus Kleine
Johannes Kaesmacher
Claus Zimmer
Lucas Schirmer
Sophie Simon
Holger Poppert
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Thrombosis Journal / Issue 1/2017
Electronic ISSN: 1477-9560
DOI
https://doi.org/10.1186/s12959-017-0134-4

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