title: Imaging of a clinically relevant stroke model: glucose hypermetabolism revisited.
abstract: OBJECTIVE
  Ischemic stroke has been shown to cause hypermetabolism of glucose in the ischemic penumbra. Experimental and clinical data indicate that infarct-related systemic hyperglycemia is a potential therapeutic target in acute stroke. However, clinical studies aiming for glucose control in acute stroke have neither improved functional outcome nor reduced mortality. Thus, further studies on glucose metabolism in the ischemic brain are warranted.
  
  
  METHODS
  We used a rat model of stroke that preserves collateral flow. The animals were analyzed by [2-(18)F]-2-fluoro-2-deoxy-d-glucose positron emission tomography or magnetic resonance imaging during 90-minute occlusion of the middle cerebral artery and during 60 minutes after reperfusion. Results were correlated to magnetic resonance imaging of cerebral blood flow, diffusion of water, lactate formation, and histological data on cell death and blood-brain barrier breakdown.
  
  
  RESULTS
  We detected an increased [2-(18)F]-2-fluoro-2-deoxy-d-glucose uptake within ischemic regions succumbing to infarction and in the peri-infarct region. Magnetic resonance imaging revealed impairment of blood flow to ischemic levels in the infarct and a reduction of cerebral blood flow in the peri-infarct region. Magnetic resonance spectroscopy revealed lactate in the ischemic region and absence of lactate in the peri-infarct region. Immunohistochemical analyses revealed apoptosis and blood-brain barrier breakdown within the infarct.
  
  
  CONCLUSIONS
  The increased uptake of [2-(18)F]-2-fluoro-2-deoxy-d-glucose in cerebral ischemia most likely reflects hypermetabolism of glucose meeting increased energy needs of ischemic and hypoperfused brain tissue, and it occurs under both anaerobic and aerobic conditions measured by local lactate production. Infarct-related systemic hyperglycemia could serve to facilitate glucose supply to the ischemic brain. Glycemic control by insulin treatment could negatively influence this mechanism.
authors: From the Department of Clinical Neuroscience (F.A., J.G., J.L., P.L., M.S., S.S.-E., S.H.), Karolinska Experimental Research and Imaging Center (KERIC) (S.N.-A., P.D., L.L.), Science for Life Laboratory, Department of Neuroscience (N.M., J.M.), Karolinska Institutet, Stockholm, Sweden; and Department of Neuroradiology (F.A., J.L., P.L., M.S., S.S.-E., S.H.), Department of Radiology (F.A.), Karolinska University Hospital-Solna, Stockholm, Sweden.
authors: Fabian
authors: F
authors: Arnberg
authors: From the Department of Clinical Neuroscience (F.A., J.G., J.L., P.L., M.S., S.S.-E., S.H.), Karolinska Experimental Research and Imaging Center (KERIC) (S.N.-A., P.D., L.L.), Science for Life Laboratory, Department of Neuroscience (N.M., J.M.), Karolinska Institutet, Stockholm, Sweden; and Department of Neuroradiology (F.A., J.L., P.L., M.S., S.S.-E., S.H.), Department of Radiology (F.A.), Karolinska University Hospital-Solna, Stockholm, Sweden.
authors: Jonas
authors: J
authors: Grafström
authors: From the Department of Clinical Neuroscience (F.A., J.G., J.L., P.L., M.S., S.S.-E., S.H.), Karolinska Experimental Research and Imaging Center (KERIC) (S.N.-A., P.D., L.L.), Science for Life Laboratory, Department of Neuroscience (N.M., J.M.), Karolinska Institutet, Stockholm, Sweden; and Department of Neuroradiology (F.A., J.L., P.L., M.S., S.S.-E., S.H.), Department of Radiology (F.A.), Karolinska University Hospital-Solna, Stockholm, Sweden.
authors: Johan
authors: J
authors: Lundberg
authors: From the Department of Clinical Neuroscience (F.A., J.G., J.L., P.L., M.S., S.S.-E., S.H.), Karolinska Experimental Research and Imaging Center (KERIC) (S.N.-A., P.D., L.L.), Science for Life Laboratory, Department of Neuroscience (N.M., J.M.), Karolinska Institutet, Stockholm, Sweden; and Department of Neuroradiology (F.A., J.L., P.L., M.S., S.S.-E., S.H.), Department of Radiology (F.A.), Karolinska University Hospital-Solna, Stockholm, Sweden.
authors: Sahar
authors: S
authors: Nikkhou-Aski
authors: From the Department of Clinical Neuroscience (F.A., J.G., J.L., P.L., M.S., S.S.-E., S.H.), Karolinska Experimental Research and Imaging Center (KERIC) (S.N.-A., P.D., L.L.), Science for Life Laboratory, Department of Neuroscience (N.M., J.M.), Karolinska Institutet, Stockholm, Sweden; and Department of Neuroradiology (F.A., J.L., P.L., M.S., S.S.-E., S.H.), Department of Radiology (F.A.), Karolinska University Hospital-Solna, Stockholm, Sweden.
authors: Philip
authors: P
authors: Little
authors: From the Department of Clinical Neuroscience (F.A., J.G., J.L., P.L., M.S., S.S.-E., S.H.), Karolinska Experimental Research and Imaging Center (KERIC) (S.N.-A., P.D., L.L.), Science for Life Laboratory, Department of Neuroscience (N.M., J.M.), Karolinska Institutet, Stockholm, Sweden; and Department of Neuroradiology (F.A., J.L., P.L., M.S., S.S.-E., S.H.), Department of Radiology (F.A.), Karolinska University Hospital-Solna, Stockholm, Sweden.
authors: Peter
authors: P
authors: Damberg
authors: From the Department of Clinical Neuroscience (F.A., J.G., J.L., P.L., M.S., S.S.-E., S.H.), Karolinska Experimental Research and Imaging Center (KERIC) (S.N.-A., P.D., L.L.), Science for Life Laboratory, Department of Neuroscience (N.M., J.M.), Karolinska Institutet, Stockholm, Sweden; and Department of Neuroradiology (F.A., J.L., P.L., M.S., S.S.-E., S.H.), Department of Radiology (F.A.), Karolinska University Hospital-Solna, Stockholm, Sweden.
authors: Nicholas
authors: N
authors: Mitsios
authors: From the Department of Clinical Neuroscience (F.A., J.G., J.L., P.L., M.S., S.S.-E., S.H.), Karolinska Experimental Research and Imaging Center (KERIC) (S.N.-A., P.D., L.L.), Science for Life Laboratory, Department of Neuroscience (N.M., J.M.), Karolinska Institutet, Stockholm, Sweden; and Department of Neuroradiology (F.A., J.L., P.L., M.S., S.S.-E., S.H.), Department of Radiology (F.A.), Karolinska University Hospital-Solna, Stockholm, Sweden.
authors: Jan
authors: J
authors: Mulder
authors: From the Department of Clinical Neuroscience (F.A., J.G., J.L., P.L., M.S., S.S.-E., S.H.), Karolinska Experimental Research and Imaging Center (KERIC) (S.N.-A., P.D., L.L.), Science for Life Laboratory, Department of Neuroscience (N.M., J.M.), Karolinska Institutet, Stockholm, Sweden; and Department of Neuroradiology (F.A., J.L., P.L., M.S., S.S.-E., S.H.), Department of Radiology (F.A.), Karolinska University Hospital-Solna, Stockholm, Sweden.
authors: Li
authors: L
authors: Lu
authors: From the Department of Clinical Neuroscience (F.A., J.G., J.L., P.L., M.S., S.S.-E., S.H.), Karolinska Experimental Research and Imaging Center (KERIC) (S.N.-A., P.D., L.L.), Science for Life Laboratory, Department of Neuroscience (N.M., J.M.), Karolinska Institutet, Stockholm, Sweden; and Department of Neuroradiology (F.A., J.L., P.L., M.S., S.S.-E., S.H.), Department of Radiology (F.A.), Karolinska University Hospital-Solna, Stockholm, Sweden.
authors: Michael
authors: M
authors: Söderman
authors: From the Department of Clinical Neuroscience (F.A., J.G., J.L., P.L., M.S., S.S.-E., S.H.), Karolinska Experimental Research and Imaging Center (KERIC) (S.N.-A., P.D., L.L.), Science for Life Laboratory, Department of Neuroscience (N.M., J.M.), Karolinska Institutet, Stockholm, Sweden; and Department of Neuroradiology (F.A., J.L., P.L., M.S., S.S.-E., S.H.), Department of Radiology (F.A.), Karolinska University Hospital-Solna, Stockholm, Sweden.
authors: Sharon
authors: S
authors: Stone-Elander
authors: From the Department of Clinical Neuroscience (F.A., J.G., J.L., P.L., M.S., S.S.-E., S.H.), Karolinska Experimental Research and Imaging Center (KERIC) (S.N.-A., P.D., L.L.), Science for Life Laboratory, Department of Neuroscience (N.M., J.M.), Karolinska Institutet, Stockholm, Sweden; and Department of Neuroradiology (F.A., J.L., P.L., M.S., S.S.-E., S.H.), Department of Radiology (F.A.), Karolinska University Hospital-Solna, Stockholm, Sweden. staffan.holmin@ki.se.
authors: Staffan
authors: S
authors: Holmin
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000473:pathology; D020520:Brain Infarction / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology; D007511:Ischemia; D007773:Lactates / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000097:blood* / Q000503:physiopathology*
chemical_list: D001786:Blood Glucose; D007773:Lactates; D019788:Fluorodeoxyglucose F18; D005947:Glucose
keywords: diffusion magnetic resonance imaging; glucose; infarction; stroke