Effects of 2-deoxy-d-glucose on focal cerebral ischemia in hyperglycemic rats.
The authors 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 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, gradient echo bolus tracking, steady-state spin echo imaging, and water-suppressed proton magnetic resonance spectroscopy techniques, the time course of the early changes of the lactate/NAA peak ratio and perfusion deficit was examined in hyperglycemic rats undergoing 90-minute MCAO followed by 24-h reperfusion. Compared with the saline-treated hyperglycemic rats, 2DG treatment at 10 minutes before MCAO significantly reduced diffusion weighted imaging hyperintensity by approximately 60% and the lactate/NAA peak ratio by approximately 70% at 4 h after MCAO/R. Both spin echo-measured cerebral blood volume and dynamic gradient echo-relative cerebral blood flow showed that the restoration of blood supply recovered and remained at approximately 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.
Wei
Jingna
J
Marine Biomedical Institute, Department of Anatomy, University of Texas Medical Branch, Galveston, Texas 77555, U.S.A.
Cohen
David M
DM
Quast
Michael J
MJ
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D019344:Lactic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley
D000963:Antimetabolites; D011522:Protons; D001224:Aspartic Acid; D019344:Lactic Acid; C000179:N-acetylaspartate; D003847:Deoxyglucose