Objective: To develop oxygen/glucose deprivation (OGD)- and NMDA-induced neurotoxicity models in rat primary
neurons and
hippocampal slices, and to determine the protective
effect of
minocycline. Methods: The injuries of primary neurons were induced by OGD or NMDA (50 μmol/L). Morphological changes of neurons were observed, and neuron viability was evaluated by MTT assay. The changes of light transmittance (
LT) were induced by OGD or NMDA in rat hippocampal slices. The effects of minocycline and MK-801, an NMDA receptor antagonist, were observed in the models of OGD- or NMDA-induced injuries. Results: Minocycline concentration dependently
inhibited OGD-induced decrease of neuron viability and ameliorated neuron morphological changes at 1 and 10 μmol/L. It also inhibited NMDA insult at 10 and 100 μmol/L. MK-801 inhibited both injuries at 1 μmol/L. However, minocycline at 1 or 10 μmol/L did not inhibit the augment of LT in hippocampal slices induced by OGD or NMDA, while MK-801 inhibited both OGD- and NMDA-induced LT augments. Conclusion: Minocycline protects neurons from OGD insult, which may inhibit NMDA receptor-mediated neurotoxicity through an indirect pathway, but has no effect on OGD- or NMDA-induced immediate injury in hippocampal slices.