Effects of 2-Deoxyglucose on ischemic brain injuries in rats

Int J Neurosci. 2014 Sep;124(9):666-72. doi: 10.3109/00207454.2013.868807. Epub 2014 Jan 7.

Abstract

Objectives: In vivo and in vitro studies have shown that 2-deoxyglucose (2-DG) administration enhances tolerance and exerts neuroprotection against ischemic injury or oxidative stress. In this study, we investigated the effects of 2-DG on ischemic brain injuries in rats and determined whether the effects are related to sublethal endoplasmic reticulum (ER) stress.

Methods: 2-DG was administered systemically 7 d before the rats were subjected to focal cerebral ischemia (2 h) followed by reperfusion. Neurological score and infarct volume were evaluated, and protein expression of ER molecular chaperone glucose-regulated protein 78 (GRP78) and X-box protein-1 (XBP-1) was determined at different time points after reperfusion.

Results: 2-DG pretreatment significantly decreased neurological scores after reperfusion for 3 h, 6 h, 12 h, and 24 h, reduced infarct volume at 24 h after reperfusion compared to the corresponding control groups. ER molecular chaperone GRP78 and XBP-1 increased in 2-DG pretreatment group as compared to the control.

Conclusion: Pretreatment with 2-DG improves the neurological function after cerebral ischemia-reperfusion injury. Increased expression of ER chaperone GRP78 and activation of XBP-1 may contribute to the protective effect of 2-DG against brain injury.

Keywords: 2-deoxyglucose; brain injury; ischemia; rats; reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Antimetabolites / pharmacology
  • Antimetabolites / therapeutic use*
  • Brain Injuries / etiology*
  • Brain Injuries / prevention & control*
  • DNA-Binding Proteins / metabolism
  • Deoxyglucose / pharmacology
  • Deoxyglucose / therapeutic use*
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Heat-Shock Proteins / metabolism
  • Infarction, Middle Cerebral Artery / complications*
  • Infarction, Middle Cerebral Artery / prevention & control
  • Male
  • Nervous System Diseases / etiology
  • Nervous System Diseases / prevention & control
  • Neurologic Examination
  • Phosphopyruvate Hydratase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Regulatory Factor X Transcription Factors
  • Reperfusion
  • Time Factors
  • Transcription Factors / metabolism
  • X-Box Binding Protein 1

Substances

  • Antimetabolites
  • DNA-Binding Proteins
  • GRP78 protein, rat
  • Heat-Shock Proteins
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • Xbp1 protein, rat
  • Deoxyglucose
  • Phosphopyruvate Hydratase