Inflammatory Response of Ischemic Tolerance in Circulating Plasma: Preconditioning-Induced by Transient Ischemic Attack (TIA) Phenomena in Acute Ischemia Patients (AIS)

Introduction: Ischemic tolerance (IT) refers to a state where cells are resistant to the damaging effects caused by periods of ischemia. In a clinical scenario, the IT phenomenon would be activated by a recent transient ischemic attack (TIA) before an ischemic stroke (IS). The characterization of in...

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Main Authors: Laura Colàs-Campàs, Joan Farre, Gerard Mauri-Capdevila, Jessica Molina-Seguín, Núria Aymerich, Ángel Ois, Jaume Roquer, Silvia Tur, María del Carmen García-Carreira, Joan Martí-Fàbregas, Antonio Cruz-Culebras, Tomás Segura, Gloria Arque, Francisco Purroy
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-10-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2020.552470/full
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author Laura Colàs-Campàs
Joan Farre
Joan Farre
Gerard Mauri-Capdevila
Gerard Mauri-Capdevila
Jessica Molina-Seguín
Núria Aymerich
Ángel Ois
Jaume Roquer
Silvia Tur
María del Carmen García-Carreira
Joan Martí-Fàbregas
Antonio Cruz-Culebras
Tomás Segura
Gloria Arque
Francisco Purroy
Francisco Purroy
author_facet Laura Colàs-Campàs
Joan Farre
Joan Farre
Gerard Mauri-Capdevila
Gerard Mauri-Capdevila
Jessica Molina-Seguín
Núria Aymerich
Ángel Ois
Jaume Roquer
Silvia Tur
María del Carmen García-Carreira
Joan Martí-Fàbregas
Antonio Cruz-Culebras
Tomás Segura
Gloria Arque
Francisco Purroy
Francisco Purroy
author_sort Laura Colàs-Campàs
collection DOAJ
description Introduction: Ischemic tolerance (IT) refers to a state where cells are resistant to the damaging effects caused by periods of ischemia. In a clinical scenario, the IT phenomenon would be activated by a recent transient ischemic attack (TIA) before an ischemic stroke (IS). The characterization of inflammatory protein expression patterns will contribute to improved understanding of IT.Methods: A total of 477 IS patients from nine hospitals, recruited between January 2011 and January 2016, were included in the current study and divided in three groups: 438 (91.9%) patients without previous TIA (group 1), 22 (4.6%) patients who suffered TIA 24 h before IS (group 2), and 17 (3.5%) patients who suffered TIA between 24 h and 7 days prior to IS (group 3). An inflammatory biomarker panel (IL-6, NT-proBNP, hsCRP, hs-Troponin, NSE, and S-100b) on plasma and a cytokine antibody array was performed to achieve the preconditioning signature potentially induced by TIA phenomena. Primary outcome was modified rankin scale (mRs) score at 90 days.Results: Recent previous TIA was associated with better clinical outcome at 90 days (median mRS of group 1: 2.0 [1.0–4.0]; group 2: 2.0 [0.0–3.0]; group 3: 1.0 [0–2.5]; p = 0.086) and smaller brain lesion (group 1: 3.7 [0.7–18.3]; group 2: 0.8 [0.3–8.9]; group 3: 0.6 [0.1–5.5] mL; p = 0.006). All inflammation biomarkers were down regulated in the groups of recent TIA prior to IS compared to those who did not suffer a TIA events. Moreover, a cytokine antibody array revealed 30 differentially expressed proteins between the three groups. Among them, HRG1-alpha (Fold change 74.4 between group 1 and 2; 74.2 between group 1 and 3) and MAC-1 (Fold change 0.05 between group 1 and 2; 0.06 between group 1 and 3) expression levels would better stratify patients with TIA 7 days before IS. These two proteins showed an earlier inflammation profile that was not detectable by the biomarker panel.Conclusion: Inflammatory pathways were activated by transient ischemic attack, however the period of time between this event and a further ischemic stroke could be determined by a protein signature that would contribute to define the role of ischemic tolerance induced by TIA.
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spelling doaj.art-02b8ab2adb0d467ebf1996a5327166fe2022-12-22T00:30:09ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-10-011110.3389/fneur.2020.552470552470Inflammatory Response of Ischemic Tolerance in Circulating Plasma: Preconditioning-Induced by Transient Ischemic Attack (TIA) Phenomena in Acute Ischemia Patients (AIS)Laura Colàs-Campàs0Joan Farre1Joan Farre2Gerard Mauri-Capdevila3Gerard Mauri-Capdevila4Jessica Molina-Seguín5Núria Aymerich6Ángel Ois7Jaume Roquer8Silvia Tur9María del Carmen García-Carreira10Joan Martí-Fàbregas11Antonio Cruz-Culebras12Tomás Segura13Gloria Arque14Francisco Purroy15Francisco Purroy16Clinical Neurosciences Group, Institut de Recerca Biomèdica de Lleida, Lleida, SpainClinical Neurosciences Group, Institut de Recerca Biomèdica de Lleida, Lleida, SpainMedical Laboratory, Hospital Universitari Arnau de Vilanova, Lleida, SpainClinical Neurosciences Group, Institut de Recerca Biomèdica de Lleida, Lleida, SpainStroke Unit, Department of Neurology, Hospital Universitari Arnau de Vilanova, Lleida, SpainClinical Neurosciences Group, Institut de Recerca Biomèdica de Lleida, Lleida, SpainComplejo Hospitalario de Navarra, Pamplona, SpainHospital del Mar, Barcelona, SpainHospital del Mar, Barcelona, SpainHospital Son Espases, Palma de Mallorca, SpainCorporació Sanitària Parc Taulí, Sabadell, SpainHospital de la Santa Creu i Sant Pau, Barcelona, SpainHospital Universitario Ramón y Cajal, Madrid, Spain0Complejo Hospitalario Universitario de Albacete, Albacete, SpainClinical Neurosciences Group, Institut de Recerca Biomèdica de Lleida, Lleida, SpainClinical Neurosciences Group, Institut de Recerca Biomèdica de Lleida, Lleida, SpainStroke Unit, Department of Neurology, Hospital Universitari Arnau de Vilanova, Lleida, SpainIntroduction: Ischemic tolerance (IT) refers to a state where cells are resistant to the damaging effects caused by periods of ischemia. In a clinical scenario, the IT phenomenon would be activated by a recent transient ischemic attack (TIA) before an ischemic stroke (IS). The characterization of inflammatory protein expression patterns will contribute to improved understanding of IT.Methods: A total of 477 IS patients from nine hospitals, recruited between January 2011 and January 2016, were included in the current study and divided in three groups: 438 (91.9%) patients without previous TIA (group 1), 22 (4.6%) patients who suffered TIA 24 h before IS (group 2), and 17 (3.5%) patients who suffered TIA between 24 h and 7 days prior to IS (group 3). An inflammatory biomarker panel (IL-6, NT-proBNP, hsCRP, hs-Troponin, NSE, and S-100b) on plasma and a cytokine antibody array was performed to achieve the preconditioning signature potentially induced by TIA phenomena. Primary outcome was modified rankin scale (mRs) score at 90 days.Results: Recent previous TIA was associated with better clinical outcome at 90 days (median mRS of group 1: 2.0 [1.0–4.0]; group 2: 2.0 [0.0–3.0]; group 3: 1.0 [0–2.5]; p = 0.086) and smaller brain lesion (group 1: 3.7 [0.7–18.3]; group 2: 0.8 [0.3–8.9]; group 3: 0.6 [0.1–5.5] mL; p = 0.006). All inflammation biomarkers were down regulated in the groups of recent TIA prior to IS compared to those who did not suffer a TIA events. Moreover, a cytokine antibody array revealed 30 differentially expressed proteins between the three groups. Among them, HRG1-alpha (Fold change 74.4 between group 1 and 2; 74.2 between group 1 and 3) and MAC-1 (Fold change 0.05 between group 1 and 2; 0.06 between group 1 and 3) expression levels would better stratify patients with TIA 7 days before IS. These two proteins showed an earlier inflammation profile that was not detectable by the biomarker panel.Conclusion: Inflammatory pathways were activated by transient ischemic attack, however the period of time between this event and a further ischemic stroke could be determined by a protein signature that would contribute to define the role of ischemic tolerance induced by TIA.https://www.frontiersin.org/articles/10.3389/fneur.2020.552470/fullischemic stroketransient ischemic attack (TIA)plasmaischemic preconditioning (IPC)endogenous neuroprotectionbiomarker (BM)
spellingShingle Laura Colàs-Campàs
Joan Farre
Joan Farre
Gerard Mauri-Capdevila
Gerard Mauri-Capdevila
Jessica Molina-Seguín
Núria Aymerich
Ángel Ois
Jaume Roquer
Silvia Tur
María del Carmen García-Carreira
Joan Martí-Fàbregas
Antonio Cruz-Culebras
Tomás Segura
Gloria Arque
Francisco Purroy
Francisco Purroy
Inflammatory Response of Ischemic Tolerance in Circulating Plasma: Preconditioning-Induced by Transient Ischemic Attack (TIA) Phenomena in Acute Ischemia Patients (AIS)
Frontiers in Neurology
ischemic stroke
transient ischemic attack (TIA)
plasma
ischemic preconditioning (IPC)
endogenous neuroprotection
biomarker (BM)
title Inflammatory Response of Ischemic Tolerance in Circulating Plasma: Preconditioning-Induced by Transient Ischemic Attack (TIA) Phenomena in Acute Ischemia Patients (AIS)
title_full Inflammatory Response of Ischemic Tolerance in Circulating Plasma: Preconditioning-Induced by Transient Ischemic Attack (TIA) Phenomena in Acute Ischemia Patients (AIS)
title_fullStr Inflammatory Response of Ischemic Tolerance in Circulating Plasma: Preconditioning-Induced by Transient Ischemic Attack (TIA) Phenomena in Acute Ischemia Patients (AIS)
title_full_unstemmed Inflammatory Response of Ischemic Tolerance in Circulating Plasma: Preconditioning-Induced by Transient Ischemic Attack (TIA) Phenomena in Acute Ischemia Patients (AIS)
title_short Inflammatory Response of Ischemic Tolerance in Circulating Plasma: Preconditioning-Induced by Transient Ischemic Attack (TIA) Phenomena in Acute Ischemia Patients (AIS)
title_sort inflammatory response of ischemic tolerance in circulating plasma preconditioning induced by transient ischemic attack tia phenomena in acute ischemia patients ais
topic ischemic stroke
transient ischemic attack (TIA)
plasma
ischemic preconditioning (IPC)
endogenous neuroprotection
biomarker (BM)
url https://www.frontiersin.org/articles/10.3389/fneur.2020.552470/full
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