Effects of 2-Deoxy-D-glucose on focal cerebral ischemia in hyperglycemic rats

Abstract

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 ∼60% and the lactate/NAA peak ratio by ∼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 ∼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.