EFFECT OF CHRONIC EXPOSURE TO HIGH MAGNESIUM ON NEURON SURVIVAL IN LONG-TERM NEOCORTICAL EXPLANTS OF NEONATAL RATS INVITRO

In order to assess the effect of elevated magnesium, neuronal morphology and physiology was studied in chronically cultured organotypic neonatal rat occipital neocortex. Explants grown in 10 mM magnesium were found to experience an approximate 30% cell loss (as shown by cell count and DNA-protein analysis), while 12.5 and 15 mM magnesium showed ca. 47 and 60% cell losses, respectively, Intracellular recording from 10 mM magnesium explants revealed that measurable postsynaptic potentials and action potentials could occur, apparently depending on the type of cell examined. All post-synaptic activities ceased in 12.5 mM magnesium cultures, though action potentials could be elicited by current stimulation. The effects of known depolarizing agents, viz. potassium and N-methyl-D-aspartate, on 12.5 mM magnesium-grown explants were also examined. Explants grown in the presence of 12.5 mM magnesium plus 10 mM potassium showed a dramatic increase in the loss of neurons. The simultaneous addition of 6,7-dinitro-quinoxaline-2,3-dione showed this to be due to an increase in non-N-methyl-D-aspartate mediated cell death in response to glutamate release brought about by the depolarizing effects of the potassium. The addition of 10-mu-M N-methyl-D-aspartate to 12.5 mM magnesium-grown cultures, on the other hand, improved cell survival to control levels. The mechanism of this reciprocal neuroprotective effect of N-methyl-D-aspartate against magnesium has yet to be elucidated. We conclude that these findings are consistent with regard to the opposing actions of N-methyl-D-aspartate and magnesium on calcium influx and various metabolic processes within the explants.