We are applying multi-nuclear high-field (500 MHz) MR spectroscopy of metabolising whole tissue preparations of the mammalian brain to studies on individual components of convulsions, which include prolonged depolarization, metabolic deprivation, and the effects of
excitotoxins. The responses of glial cells and neurones can be partially distinguished by following labelling patterns of metabolic intermediates from 13C-labelled
glucose or
acetate (which enters only glial cells). This approach clearly confirmed our earlier indications that the metabolic response to depolarization (40 mM extracellular K+) occurs essentially in glial cells. Some evidence for metabolic shuttling between glia and neurones was obtained from the changes in C3/C4 ratios of
glutamate and
glutamine, and the C2/C3 of
GABA. Mechanisms for metabolic support of neurones by glia may be of importance in neuronal protection under such metabolic stress as occurs in
epilepsy. Changes in free intracellular
divalent cations ([Ca2+]i and [Zn2+]i) were monitored using the 19F-MRS
indicator, 5FBAPTA. Large increases in [Ca2+]i and decreases in PCr were produced by
excitotoxins (
glutamate and
NMDA), depolarization or
ischemia, but intracellular Zn2+ appeared only after exposure to the
excitotoxins. The
NMDA receptor blocker,
MK801, removed all of the responses to
NMDA, but only prevented the appearance of Zn2+ observed with
glutamate. These results indicate that the damage caused to neurones by such insults as convulsions is not due simply to the presence of excessive excitotoxic
glutamate.