Neurotoxicity after hypoxia/during ischemia due to glutamate with/without free radicals as revealed by dynamic changes in glucose metabolism.
Fresh rat brain slices were incubated with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and serial two-dimensional time-resolved images of [18F]FDG uptake in the slices were obtained on imaging plates. The fractional rate constant of [18F]FDG (proportional to the cerebral glucose metabolic rate) from pre-loading of ischemia (O(2) and glucose deprivation)/hypoxia (O(2) deprivation) to the reperfused/reoxygenated post-loading phase was quantitatively evaluated by applying the Gjedde-Patlak graphical method to the image data. Against ischemia an N-methyl-D-aspartate antagonist and hypothermia, but not a free radical scavenger, showed a protective effect when administered during ischemia, whereas no such effect was achieved with any of the above agents when administered after reperfusion. Against hypoxia, there was no protective effect with any of the above agents when administered during hypoxia, although an effect was noted with each when administered after reoxygenation. Excitatory amino acids during ischemia loading were found to be the main factor in the neuronal damage associated with ischemia, while in hypoxia, excitatory amino acids working in tandem with free radicals immediately after reoxygenation were implicated.
Murata
T
T
Biomedical Imaging Research Center, Fukui Medical University, Matsuoka-cho, 910-1193, Fukui, Japan. tmurata@fmsrsa.fukui-med.ac.jp
Omata
N
N
Fujibayashi
Y
Y
Waki
A
A
Sadato
N
N
Yoshimoto
M
M
Wada
Y
Y
Yonekura
Y
Y
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D003497:Cyclic N-Oxides; D016291:Dizocilpine Maleate / Q000494:pharmacology; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism*; D007035:Hypothermia / Q000378:metabolism; D002534:Hypoxia, Brain / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D003497:Cyclic N-Oxides; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C029217:phenyl-N-tert-butylnitrone; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D005947:Glucose