title: Effects of acute and chronic hyperglycemia on the neurochemical profiles in the rat brain with streptozotocin-induced diabetes detected using in vivo ¹H MR spectroscopy at 9.4 T.
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 vivo ¹H 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.
authors.affiliation: Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Wen-Tung
authors.initials: WT
authors.lastname: Wang
authors.forename: Phil
authors.initials: P
authors.lastname: Lee
authors.forename: Hung-Wen
authors.initials: HW
authors.lastname: Yeh
authors.forename: Irina V
authors.initials: IV
authors.lastname: Smirnova
authors.forename: In-Young
authors.initials: IY
authors.lastname: Choi
mesh_terms: D000208:Acute Disease; D000465:Algorithms; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000097:blood; D001693:Biological Transport, Active / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000378:metabolism; D018450:Disease Progression; D005947:Glucose / Q000378:metabolism; D005978:Glutathione / Q000097:blood; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D001224:Aspartic Acid; C000179:N-acetylaspartate; D005978:Glutathione; D005947:Glucose