AUTHOR=Colàs-Campàs Laura , Farre Joan , Mauri-Capdevila Gerard , Molina-Seguín Jessica , Aymerich Núria , Ois Ángel , Roquer Jaume , Tur Silvia , García-Carreira María del Carmen , Martí-Fàbregas Joan , Cruz-Culebras Antonio , Segura Tomás , Arque Gloria , Purroy Francisco 

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

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.552470

DOI=10.3389/fneur.2020.552470

ISSN=1664-2295

ABSTRACT=<p><bold>Introduction:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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]; <italic>p</italic> = 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; <italic>p</italic> = 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.</p><p><bold>Conclusion:</bold> 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.</p>