Magnetic resonance spectroscopy studies on changes in cerebral calcium andzinc and the energy state caused by excitotoxic amino acids

Under control conditions, superfused hippocampal slices exhibited a signifi cantly higher phosphocreatine (PCr)/ATP ratio than cortical slices; the evi dence suggests that this is due to lower concentrations of ATP, rather than higher concentrations of PCr. Glutamate caused relatively rapid decreases in PCr and ATP levels to similar to 45%, accompanied or immediately followe d by an increased free intracellular calcium concentration ([Ca2+](i)) and the release of Zn2+ in the cortex. In the hippocampus PCr and ATP decreased further to similar to 20% of control values, but the changes in [Ca2+](i) and Zn2+ content were slower. This is in contrast to the effects of depolar isation, which produced the same rapid changes in the energy state and [Ca2 +](i), with no detectable Zn2+ in both tissues. NMDA causes effects similar to those of glutamate in the cortex (decreases in the energy stale, increa sed [Ca2+](i), and release of Zn2+). Pretreatment of the cortex for 1 h wit h the NMDA blocker MK-801 prevented all of the observed effects of NMDA. In contrast, pretreatment with MK-801 had no detectable effect on the increas e in [Ca2+](i) or the decreases in PCr and ATP caused by glutamate, althoug h it prevented the release of zinc. The results are discussed in relation t o the function of the NMDA subtype of glutamate receptor in excitotoxicity.