Deregulation of inflammatory response in the diabetic condition is associated with increased ischemic brain injury

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• 作者：Eunhee Kim ; Aaron T Tolhurst ; Sunghee Cho
• 关键词：Diabetes ; Inflammation ; Monocytes/macrophages ; Ischemic stroke ; Mice
• 刊名：Journal of Neuroinflammation
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：11
• 期：1
• 全文大小：348 KB
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• 刊物主题：Neurosciences; Neurology; Neurobiology; Immunology;
• 出版者：BioMed Central
• ISSN：1742-2094

文摘

Background Although elicited inflammation contributes to tissue injury, a certain level of inflammation is necessary for subsequent tissue repair/remodeling. Diabetes, a chronic low-grade inflammatory state, is a predisposing risk factor for stroke. The condition is associated with delayed wound healing, presumably due to disrupted inflammatory responses. With inclusion of the diabetic condition in an experimental animal model of stroke, this study investigates whether the condition alters inflammatory response and influences stroke-induced brain injury. Methods C57BL/6 mice were fed a diabetic diet (DD) for 8?weeks to induce an experimental diabetic condition or a normal diet (ND) for the same duration. Gene expression of inflammatory factors including monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), CCR2, and CD36 was assessed in the peripheral immune cells and brains of normal and diabetic mice before and after focal cerebral ischemia. The expression of these factors was also determined in lipopolysaccharide (LPS)-treated cultured normal and diabetic macrophages. Ischemic outcome was assessed in these mice at 3?days post-ischemia. Results DD intervention in mice resulted in obesity and elevated insulin and glucose level in the blood. The peritoneal immune cells from the diabetic mice showed higher MCP-1 mRNA levels before and after stroke. Compared to normal mice, diabetic mice showed reduced MCP-1, IL-6, and CCR2 gene expression in the brain at 6?h post-ischemia. LPS-stimulated inflammatory responses were also reduced in the diabetic macrophages. The diabetic mice showed larger infarct size and percent swelling. Conclusions These results showed that diabetic conditions deregulate acute inflammatory response and that the condition is associated with increased stroke-induced injury. The study suggests that interventions aimed at restoring appropriate inflammatory response in peripheral immune cells/macrophages may be beneficial in reducing stroke-induced brain injury in subjects with chronic inflammatory conditions.