Neuroprotective effects of magnesium on metabolic disturbances in fetal hippocampal slices after oxygen-glucose deprivation: mediation by nitric oxide system.

OBJECTIVE

We investigated the effects of magnesium on metabolic disturbances in hippocampal slices prepared from fetal guinea pigs after oxygen-glucose deprivation (OGD).

METHODS

Metabolic disturbances were assessed by measuring changes in energy metabolism and protein synthesis. In addition we determined cyclic guanosine monophosphate (cGMP) concentrations in the slices after OGD, as a measure of nitric oxide (NO) production, to clarify whether a possible neuroprotective effect of magnesium is mediated in part through the NO system.

RESULTS

Twelve hours after oxygen-glucose deprivation, adenosine triphosphate (ATP) concentration and protein synthesis in the hippocampal slices were significantly reduced depending on the severity of OGD. A higher magnesium concentration in the incubation medium from 1.3 mM to 3.9 mM 2 hours before OGD significantly improved the recovery of ATP and protein synthesis, whereas treatment after OGD was ineffective. The cGMP concentrations increased dramatically in hippocampal slices 10 minutes after OGD, indicating a significant increase in NO production. When the concentration of magnesium in the artificial cerebrospinal fluid was increased 2 hours before OGD the rise in tissue levels of cGMP was considerably reduced. Again, treatment after OGD had no effect.

CONCLUSION

We conclude that increasing magnesium concentration in the artificial cerebrospinal fluid before OGD alleviated metabolic disturbances in hippocampal slices from mature fetal guinea pigs, whereas treatment after OGD had no effect. This neuroprotective property of magnesium might be mediated in part through the inhibition of NO production shortly after OGD.