Dynamic changes in glucose metabolism of living rat brain slices induced by hypoxia and neurotoxic chemical-loading revealed by positron autoradiography.
Fresh rat brain slices were incubated with 2-deoxy-2-[18F]-fluoro-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and serial two-dimensional time-resolved images of [18F]FDG uptake were obtained from these specimens on imaging plates. The fractional rate constant (= k3*) of [18F]FDG proportional to the cerebral glucose metabolic rate (CMRglc) was evaluated by applying the Gjedde-Patlak graphical method to the image data. With hypoxia loading (oxygen deprivation) or glucose metabolism inhibitors acting on oxidative phosphorylation, the k3* value increased dramatically suggesting enhanced glycolysis. After relieving hypoxia < or = 10-min, the k3* value returned to the pre-loading level. In contrast, with > or = 20-min hypoxia only partial or no recovery was observed, indicating that irreversible neuronal damage had been induced. However, after loading with tetrodotoxin (TTX), the k3* value also decreased but returned to the pre-loading level even after 70-min TTX-loading, reflecting a transient inhibition of neuronal activity. This technique provides a new means of quantifying dynamic changes in the regional CMRglc in living brain slices in response to various interventions such as hypoxia and neurotoxic chemical-loading as well as determining the viability and prognosis of brain tissues.
Murata
T
T
Biomedical Imaging Research Center, and Department of Neuropsychiatry, Fukui Medical University, Japan. tmurata@fmsrsa.fukui-med.ac.jp
Omata
N
N
Fujibayashi
Y
Y
Waki
A
A
Sadato
N
N
Yoshida
S
S
Yano
R
R
Yoshimoto
M
M
Yonekura
Y
Y
D000818:Animals; D001345:Autoradiography / Q000295:instrumentation / Q000379:methods*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003470:Culture Media; D004583:Electrons; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007773:Lactates / Q000032:analysis; D008297:Male; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology
D003470:Culture Media; D007773:Lactates; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D013779:Tetrodotoxin; D005947:Glucose