title: Key Immune Events of the Pathomechanisms of Early Cardioembolic Stroke: Multi-Database Mining and Systems Biology Approach.
abstract: While inflammation has generally been regarded as a negative factor in stroke recovery, this viewpoint has recently been challenged by demonstrating that inflammation is a necessary and sufficient factor for regeneration in the zebrafish brain injury model. This close relationship with inflammation suggests that a re-examination of the immune system's role in strokes is necessary. We used a systems biology approach to investigate the role of immune-related functions via their interactions with other molecular functions in early cardioembolic stroke. Based on protein interaction models and on microarray data from the blood of stroke subjects and healthy controls, networks were constructed to delineate molecular interactions at four early stages (pre-stroke, 3 h, 5 h and 24 h after stroke onset) of cardioembolic stroke. A comparative analysis of functional networks identified interactions of immune-related functions with other molecular functions, including growth factors, neuro/hormone and housekeeping functions. These provide a potential pathomechanism for early stroke pathophysiology. In addition, several potential targets of miRNA and methylation regulations were derived based on basal level changes observed in the core networks and literature. The results provide a more comprehensive understanding of stroke progression mechanisms from an immune perspective and shed light on acute stroke treatments.
authors.affiliation: Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan. d9761820@oz.nthu.edu.tw.
authors.forename: Chia-Chou
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan. bschen@ee.nthu.edu.tw.
authors.forename: Bor-Sen
authors.initials: BS
authors.lastname: Chen
mesh_terms: D016022:Case-Control Studies; D003327:Coronary Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019175:DNA Methylation; D004617:Embolism / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics; D011485:Protein Binding; D060066:Protein Interaction Maps; D020521:Stroke / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D049490:Systems Biology
chemical_list: D035683:MicroRNAs
keywords: cardioembolic stroke; core network; functional network; immune system; inflammation; systems biology