Abstract

BACKGROUND: T cell-induced inflammatory response and related cytokine secretion at the injury site may participate in the pathogenesis of cerebral infarction. Recent studies established inducible co-stimulatory molecule (ICOS) as a novel T cell-related factor for its activation and functions. We thus investigate the role of ICOS in cerebral infarction.

MATERIAL AND METHODS: The siRNA of ICOS was first used to suppress the gene expression in cultured lymphocytes. An in vivo study was then performed by intravenous application of ICOS siRNA in cerebral infarction rats. Survival rates, neurological scores, serum tumor necrosis factor (TNF)-α, interleukin (IL)-1, and IL-17 levels were observed.

RESULTS: The expression of ICOS in cultured lymphocytes was significantly suppressed by siRNA. In the in vivo study, the application of siRNA effectively lowered mortality rates of rats, in addition to the improvement of neurological behaviors and amelioration of cerebral tissue damage. Serum levels of TNF-α, IL-1 and IL-17 were all significantly suppressed after siRNA injection.

CONCLUSIONS: ICOS siRNA can protect brain tissues from ischemia injuries after cerebral infarction, improve limb movement and coordination, lower the mortality rate of rats, and inhibit T cell-induced cytokines. These results collectively suggest the potential treatment efficacy of ICOS siRNA against cerebral infarction.

Keywords: Cells, Cultured, Cerebral Infarction - pathology, Enzyme-Linked Immunosorbent Assay, Gene Expression Profiling, Gene Expression Regulation, Inducible T-Cell Co-Stimulator Protein - metabolism, Infusions, Intravenous, Interleukin-1 - metabolism, Interleukin-17 - metabolism, Lymphocytes - metabolism, RNA, Small Interfering - metabolism, T-Lymphocytes - cytology, Tumor Necrosis Factor-alpha - metabolism