Inhibiting HMGB1 Reduces Cerebral Ischemia Reperfusion Injury in Diabetic Mice

Inflammation. 2016 Dec;39(6):1862-1870. doi: 10.1007/s10753-016-0418-z.

Abstract

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.

Keywords: HMGB1; brain ischemia reperfusion; diabetes mellitus.

MeSH terms

  • Animals
  • Antibodies / administration & dosage
  • Antibodies / therapeutic use
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / prevention & control
  • Diabetes Mellitus, Experimental / complications*
  • HMGB1 Protein / antagonists & inhibitors*
  • HMGB1 Protein / blood
  • HMGB1 Protein / immunology
  • Infarction, Middle Cerebral Artery
  • Inflammation
  • Mice
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / prevention & control

Substances

  • Antibodies
  • HMGB1 Protein