MRS studies on cerebral metabolism in intact tissues

Abstract

Use of combinations of multiply-labelled precursors ([1-13C] glucose, [2-13C] glucose, [2-13C] acetate and [1,2-13C] acetate), with analyses of isotopomers of resonances in 13C-MR spectra, is proving to be a promising approach to investigating metabolic trafficking betweeen neurones and glia in intact brain preparations. Parallel measurements of the energy state, [Ca2+]i and [Zn2+]i in superfused cerebral slices are performed using 31P- and 19F-MRS. The isotopomer analyses provided evidence for lactate production from glutamate in glia under normal conditions, and changes in the balance between neuronal and glial metabolism during depolarization. Deprivation of glucose and/or O2 gave evidence of metabolic adaptation, and hypoxia caused a diversion of glycolysis to glycerol 3-phosphate, thought to occur in glia. Exposure to excitotoxins resulted in less severe changes in [Ca2+]i and PCr than fuel deprivation or complete ischaemia, and caused release of zinc (possibly neuroprotective). The NMDA receptor blocker (MK801) reversed all of the effects of NMDA but not of glutamate or the other insults.