title: Hyperglycemia accelerates apparent diffusion coefficient-defined lesion growth after focal cerebral ischemia in rats with and without features of metabolic syndrome.
abstract: Poststroke hyperglycemia is associated with a poor outcome yet clinical management is inadequately informed. We sought to determine whether clinically relevant levels of hyperglycemia exert detrimental effects on the early evolution of focal ischemic brain damage, as determined by magnetic resonance imaging, in normal rats and in those modeling the 'metabolic syndrome'. Wistar Kyoto (WKY) or fructose-fed spontaneously hypertensive stroke-prone (ffSHRSP) rats were randomly allocated to groups for glucose or vehicle administration before permanent middle cerebral artery occlusion. Diffusion-weighted imaging was carried out over the first 4 hours after middle cerebral artery occlusion and lesion volume calculated from apparent diffusion coefficient maps. Infarct volume and immunostaining for markers of oxidative stress were measured in the fixed brain sections at 24 hours. Hyperglycemia rapidly exacerbated early ischemic damage in both WKY and ffSHRSP rats but increased infarct volume only in WKY rats. There was only limited evidence of oxidative stress in hyperglycemic animals. Acute hyperglycemia, at clinically relevant levels, exacerbates early ischemic damage in both normal and metabolic syndrome rats. Management of hyperglycemia may have greatest benefit when performed in the acute phase after stroke in the absence or presence of comorbidities.
authors.affiliation: Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: David
authors.initials: D
authors.lastname: Tarr
authors.forename: Delyth
authors.initials: D
authors.lastname: Graham
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Roy
authors.forename: William M
authors.initials: WM
authors.lastname: Holmes
authors.forename: Christopher
authors.initials: C
authors.lastname: McCabe
authors.forename: I
authors.initials: I
authors.lastname: Mhairi Macrae
authors.forename: Keith W
authors.initials: KW
authors.lastname: Muir
authors.forename: Deborah
authors.initials: D
authors.lastname: Dewar
mesh_terms: D000818:Animals; D038524:Diffusion Magnetic Resonance Imaging; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY