Effects of acute and chronic hyperglycemia on the neurochemical profiles in the rat brain with streptozotocin-induced diabetes detected using in vivo1H MR spectroscopy at 9.4 T

Authors

  • Wen-Tung Wang,

    1. Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, Kansas, USA
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  • Phil Lee,

    1. Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, Kansas, USA
    2. The Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA
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  • Hung-Wen Yeh,

    1. The Department of Biostatistics, University of Kansas Medical Center, Kansas City, Kansas, USA
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  • Irina V. Smirnova,

    1. The Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, Kansas, USA
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  • In-Young Choi

    1. Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, Kansas, USA
    2. The Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA
    3. The Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA
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Address correspondence and reprints requests to In-Young Choi, Hoglund Brain Imaging Center, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. E-mail: ichoi@kumc.edu

Abstract

J. Neurochem. (2012) 121, 407–417.

Abstract

Chronic hyperglycemia could lead to cerebral metabolic alterations and CNS injury. However, findings of metabolic alterations in poorly managed diabetes in humans and animal models are rather inconsistent. We have characterized the cerebral metabolic consequences of untreated hyperglycemia from the onset to the chronic stage in a streptozotocin-induced rat model of diabetes. In vivo1H magnetic resonance spectroscopy was used to measure over 20 neurochemicals longitudinally. Upon the onset of hyperglycemia (acute state), increases in brain glucose levels were accompanied by increases in osmolytes and ketone bodies, all of which remained consistently high through the chronic state of over 10 weeks of hyperglycemia. Only after over 4 weeks of hyperglycemia, the levels of other neurochemicals including N-acetylaspartate and glutathione were significantly reduced and these alterations persisted into the chronic stage. However, glucose transport was not altered in chronic hyperglycemia of over 10 weeks. When glucose levels were acutely restored to euglycemia, some neurochemical changes were irreversible, indicating the impact of prolonged uncontrolled hyperglycemia on the CNS. Furthermore, progressive changes in neurochemical levels from control to acute and chronic conditions demonstrated the utility of 1H magnetic resonance spectroscopy as a non-invasive tool in monitoring the disease progression in diabetes.

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