title: Hypoxic but not ischemic neurotoxicity of free radicals revealed by dynamic changes in glucose metabolism of fresh rat brain slices on positron autoradiography.
abstract: Dynamic changes in the regional cerebral glucose metabolic rate induced by hypoxia/reoxygenation or ischemia/reperfusion were investigated with a positron autoradiography technique. 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. In the case of loading hypoxia (oxygen deprivation)/pseudoischemia (oxygen and glucose deprivation) for various periods of time, the net influx constant (K) of [18F]FDG at preloading and after reoxygenation/pseudoreperfusion (post-loading) was quantitatively evaluated by applying the Patlak graphical method to the image data. Regardless of the brain region, with hypoxia lasting > or =20 minutes, the postloading K value was decreased compared with the unloaded control, whereas with pseudoischemia of < or =40 minutes, approximately the same level as the unloaded control was maintained. Next, the neuroprotective effect against hypoxia/pseudoischemia loading induced by the addition of a free radical scavenger or an N-methyl-D-aspartate (NMDA) antagonist was assessed by determining whether a decrease in the postloading K value was prevented. Whereas with 20-minute hypoxia, both agents exhibited a neuroprotective effect, in the case of 50-minute pseudoischemia, only the NMDA antagonist did so, with the free radical scavenger being ineffective. These results demonstrate that hypoxia causes irreversible neuronal damage within a shorter period than ischemia, with both free radicals and glutamate suggested to be involved in tandem in the neurotoxicity induced by hypoxia, whereas glutamate alone is involved in ischemic neurotoxicity.
authors.affiliation: Biomedical Imaging Research Center, Fukui Medical University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Omata
authors.forename: T
authors.initials: T
authors.lastname: Murata
authors.forename: Y
authors.initials: Y
authors.lastname: Fujibayashi
authors.forename: A
authors.initials: A
authors.lastname: Waki
authors.forename: N
authors.initials: N
authors.lastname: Sadato
authors.forename: M
authors.initials: M
authors.lastname: Yoshimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Wada
authors.forename: Y
authors.initials: Y
authors.lastname: Yonekura
mesh_terms: D000818:Animals; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003497:Cyclic N-Oxides; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019788:Fluorodeoxyglucose F18; D005609:Free Radicals / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009498:Neurotoxins / Q000378:metabolism; D009589:Nitrogen Oxides / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D013113:Spin Labels
chemical_list: D003497:Cyclic N-Oxides; D018691:Excitatory Amino Acid Antagonists; D005609:Free Radicals; D009498:Neurotoxins; D009589:Nitrogen Oxides; D013113:Spin Labels; D019788:Fluorodeoxyglucose F18; C029217:phenyl-N-tert-butylnitrone; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D005947:Glucose; D010100:Oxygen