Research Article: Immunological Profile of Silent Brain Infarction and Lacunar Stroke

Date Published: July 9, 2013

Publisher: Public Library of Science

Author(s): Paola Sarchielli, Katiuscia Nardi, Davide Chiasserini, Paolo Eusebi, Michela Tantucci, Vittorio Di Piero, Marta Altieri, Carmine Marini, Tommasina Russo, Mauro Silvestrini, Isabella Paolino, Paolo Calabresi, Lucilla Parnetti, Sven G. Meuth.


Neuroinflammation is believed to be involved in the pathophysiological mechanisms of silent brain infarcts (SBI). However, the immunological profile of SBI has been scarcely investigated. In the context of a national research project named SILENCE, aimed at investigating clinical, biochemical and pathogenic features of SBI, we have measured the plasma profile of some inflammatory-related molecules in SBI patients (n = 21), patients with recent lacunar infarcts (LI, n = 28) and healthy controls (n = 31), consecutively enrolled in four Italian centres. A panel of chemokines (MIG, CTACK, IL16, SDF1a, MCP1), growth factors (SCF, SCGFb, HGF, IL3), immunoglobulin-type adhesion molecules (ICAM1, VCAM1), proinflammatory cytokines (IL18, INFa2, MIF, IL12p40), cell surface receptors on T-cells (IL2Ra), and inductors of apoptosis (TRAIL) was assessed in plasma samples by Luminex xMAP™ technology. Immunological parameters were compared using non-parametric statistics and performance to distinguish SBI and LI was evaluated by receiver operating characteristic (ROC) analysis. Plasma levels of ICAM1 were significantly higher in both SBI and LI patients as compared to controls (SBI≥LI>Ctrl). A different trend was observed for IL16 (SBI

  • Ctrl), SCF (LICtrl) and SCGFb (SBI>LICtrl) and IL18 when compared to LI patients (Ctrl≤SBI>LI). All the other immunological markers did not significantly differ among groups. According to ROC analysis, the best predictor for SBI condition was the chemokine MIG (AUC = 0.84, sensitivity 86%, specificity 77%), while SCF had the best performance in distinguishing LI patients (AUC = 0.84, sensitivity 86%, specificity 68%). These results confirm the involvement of inflammatory processes in cerebrovascular disorders, particularly in SBI, a very common age-related condition. The differences in plasma profile of inflammatory molecules may underlie different pathological mechanisms in SBI and LI patients.

    Partial Text

    The term silent brain infarction (SBI) refers to cerebral infarcts detected by brain imaging in subjects without any related clinical manifestation [1]. SBI are radiologically similar to lacunar infarcts (LI). Variations of magnetic resonance imaging (MRI) characteristics and diagnostic criteria for MRI-defined SBI may lead to great discrepancies in the definition of SBI [1], [2]. In about half of published studies, SBI was defined as hypointense area on T1 and hyperintense on T2-weighted images sized ≥3 mm [1].

    In the present study, we investigated the plasma levels of a wide range of cytokines, chemokines, inflammation-related molecules, cellular receptors, inductors of apoptosis and transforming growth factors, which are involved in the immunomodulatory/inflammatory mechanisms taking place in vascular diseases (Table 4). The aim was to verify their potential involvement in cerebrovascular disorders due to cerebral small vessel disease, namely SBI and LI. We found that ICAM1,IL16, IL18, MIG. SCF, SCGFb are altered and differentially expressed in SBI and LI patients. Higher plasma levels of ICAM1, MIG and SCF better predict SBI; in this condition also levels of IL18 and SCGFb have been found significantly higher. Increased ICAM1 and IL16 as well as lower levels of both SCF and SCGFb reliably discriminate LI from SBI.