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United States Department of Agriculture

Agricultural Research Service

Title: Effects of 2-Deoxy-D-Glucose on Focal Cerebral Ischemia in Hyperglycemic Rats

Authors
item Wei, Jingna - UNIV OF TEXAS-GALVESTON
item Cohen, David
item Quast, Michael - UNIV OF TEXAS-GALVESTON

Submitted to: Journal of Cerebral Blood Flow and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: December 23, 2002
Publication Date: May 1, 2003
Citation: Wei, J., Cohen, D.M., Quast, M.J. 2003. Effects of 2-deoxy-d-glucose on focal cerebral ischemia in hyperglycemic rats. Journal of Cerebral Blood Flow and Metabolism. 23(5):556-564.

Interpretive Summary: The death of brain cells after a head injury has many causes, some of which concern changes to the chemical reactions occurring inside the cells. Based on our knowledge of the action of a particular drug (2-deoxy-D-glucose), we hypothesized that injection of that drug might protect the brain cells from dying subsequent to an injury. We tested this hypothesis on rats, and observed less damage to brain cells when this drug was given.

Technical Abstract: We examined the effects of pretreatment with 2-deoxy-D-glucose (2DG) on the middle cerebral artery occlusion/reperfusion (MCAO/R) model in hyperglycemic rats. Proton magnetic resonance imaging and spectroscopy (MRI/MRS) were used to measure the lesion size, the level of cerebral perfusion deficit, and ratio of lactate to N-acetyl aspartate (NAA) in brain regions. By performing sequential diffusion weighted imaging (DWI), gradient echo (GE) bolus tracking, steady state spin echo (SE) imaging and water-suppressed proton MRS techniques, we examined the time course of the early changes of the lactate/NAA peak ratio and perfusion deficit in the hyperglycemic rats undergoing 90 minutes MCAO followed by 24h reperfusion. Compared to the saline treated hyperglycemic rats, 2DG treatment at 10 min prior to MCAO significantly reduced DWI hyper-intensity by ~60% and the lactate/NAA peak ratio by ~70% at 4h after MCAO/R. Both SE measured cerebral blood volume (CBV) and dynamic GE relative cerebral blood flow (CBF) showed that the restoration of blood supply recovered and remained at ~80% of baseline during reperfusion in 2DG treated hyperglycemic rats. These data suggest that inhibition of glucose metabolism by 2DG has a beneficial effect in reducing brain injury and minimizing the production of brain lactate during MCAO/R in hyperglycemic rats.

Last Modified: 8/19/2014
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