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-[F-18]-fluoro-D-glucos e ([F-18]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and seri al two-dimensional time-resolved images of [F-18]FDG uptake were obtained f rom these specimens on imaging plates. The fractional rate constant (= k3*) of [F-18]FDG proportional to the cerebral glucose metabolic rate (CMRglc) was evaluated by applying the Gjedde-Patlak graphical method to the image d ata. With hypoxia loading (oxygen deprivation) or glucose metabolism inhibi tors acting on oxidative phosphorylation, the k3* value increased dramatica lly suggesting enhanced glycolysis. After relieving hypoxia less than or eq ual to 10-min, the k3* value returned to the pre-loading level. In contrast , with greater than or equal to 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 decrea sed but returned to the pre-loading level even after 70-min TTX-loading, re flecting a transient inhibition of neuronal activity. This technique provid es a new means of quantifying dynamic changes in the regional CMRglc in liv ing brain slices in response to various interventions such as hypoxia and n eurotoxic chemical-loading as well as determining the viability and prognos is of brain tissues.