Inhibiting HMGB1 Reduces Cerebral Ischemia Reperfusion Injury in Diabetic Mice

• Published in: Inflammation 2016-12, Vol.39 (6), p.1862-1870
• Main Authors: Wang, Chong, Jiang, Jie, Zhang, Xiuping, Song, Linjie, Sun, Kai, Xu, Ruxiang
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - administration & dosage; Antibodies - therapeutic use; Biomedical and Life Sciences; Biomedicine; Brain Ischemia - drug therapy; Brain Ischemia - prevention & control; Diabetes Mellitus, Experimental - complications; HMGB1 Protein - antagonists & inhibitors; HMGB1 Protein - blood; HMGB1 Protein - immunology; Immunology; Infarction, Middle Cerebral Artery; Inflammation; Internal Medicine; Mice; Original; Original Article; Pathology; Pharmacology/Toxicology; Reperfusion Injury - drug therapy; Reperfusion Injury - prevention & control; Rheumatology
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-016-0418-z

High mobility group box1 (HMGB1) promotes inflammatory injury, and accumulating evidence suggests that it plays a key role in brain ischemia reperfusion (I/R), as well as the development of diabetes mellitus (DM). The purpose of this study was to investigate whether HMGB1 plays a role in brain I/R in a DM mouse model. Diabetes mellitus was induced by a high-calorie diet and streptozotocin treatment, and cerebral ischemia was induced by middle cerebral artery occlusion. We examined HMGB1 levels following cerebral I/R injury in DM and non-DM mice and evaluated the influence of altered HMGB1 levels on the severity of cerebral injury. Serum HMGB1 levels and the inflammatory factors IL-1β, IL-6, and inflammation-related enzyme iNOS were significantly elevated in DM mice with brain I/R compared with non-DM mice with brain I/R. Blocking HMGB1 function by intraperitoneal injection of anti-HMGB1 neutralizing antibodies reversed the inflammatory response and the extent of brain damage, suggesting that HMGB1 plays an important role in cerebral ischemic stroke in diabetic mice.