Different mechanisms of hypoxic injury on white matter and gray matter as revealed by dynamic changes in glucose metabolism in rats.
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 the fractional rate constant (=k3*) of [18F]FDG proportional to the cerebral glucose metabolic rate in white matter and gray matter was investigated with positron autoradiography. In both white matter and gray matter, the k3* value with > or = 20 min hypoxia was markedly lower than the unloaded control value, indicating irreversible hypoxic injury. Next, the neuroprotective effect against hypoxia induced by the addition of an N-methyl-D-aspartate receptor antagonist or a free radical scavenger was assessed by determining whether a decrease in the k3* value after hypoxia loading was prevented. In gray matter, both agents exhibited a neuroprotective effect against 20 min hypoxia. In white matter, however, only the free radical scavenger was effective. These results suggest a similarity in the degree of vulnerability to hypoxia between white matter and gray matter as well as a difference in the developmental mechanism of hypoxic injury, i.e. the involvement of both glutamate and free radicals in gray matter, and the more selective involvement of free radicals in white matter.
Omata
Naoto
N
Department of Neuropsychiatry, Fukui Medical University, Fukui 910-1193, Japan.
Murata
Tetsuhito
T
Maruoka
Nobuyuki
N
Fujibayashi
Yasuhisa
Y
Yonekura
Yoshiharu
Y
Wada
Yuji
Y
D000818:Animals; D001345:Autoradiography; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003497:Cyclic N-Oxides; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000503:physiopathology*; D020772:Internal Capsule / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015424:Reperfusion; D013997:Time Factors
D003497:Cyclic N-Oxides; D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; D016194:Receptors, N-Methyl-D-Aspartate; D019788:Fluorodeoxyglucose F18; C029217:phenyl-N-tert-butylnitrone; D016291:Dizocilpine Maleate; D005947:Glucose