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

Journal of Neuroinflammation

Sunghee Cho¹  Aaron T Tolhurst²  Eunhee Kim¹ 

[1] Brain & Mind Research Institute, Weill Cornell Medical College at Burke Medical Research Institute, 785 Mamaroneck Ave, White Plains, NY 10605, USA;Burke-Cornell Medical Research Institute, White Plains, NY 10605, USA

关键词: Mice;    Ischemic stroke;    Monocytes/macrophages;    Inflammation;    Diabetes;   

Others  :  804384
DOI  :  10.1186/1742-2094-11-83

 received in 2014-02-04, accepted in 2014-03-26,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Kim et al.; licensee BioMed Central Ltd.

【 图 表 】

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