Effects of melatonin on cellular viability and injury induced by oxygen and glucose deprivation at different phases of co-cultured neuron and glia / 中国药理学通报

ABSTRACT

AIM To observe the effects of melatonin on acute and chronic injuries induced by oxygen and glucose deprivation (OGD) in co-cultured neuron and glia and to explore the probable mechanisms of melatonin in antagonizing the injuries. METHODS The injury model of cultured neuron and co-cultured neuron and glia was made by administration of sodium dithionite and glucose-deprived Earles solution. In neuron and glia co-culture, two different models, acute injury model at the phase of OGD and chronic injury model after 'reperfusion' were established. The levels of nitric oxide (NO) and the activity of lactate dehydrogenase (LDH) were measured by Griess reagent and LDH kits respectively. The content of malondialdehyde (MDA) was determined by TBA method. Cell viability was analyzed using colorimetric MTT assay. RESULTS Melatonin increased the level of NO at the concentration of 10 -6 , 10 -7 mol?L -1 and decreased the level of MDA content elevated by OGD at the concentration of 10 -6 , 10 -7 , 10 -8 mol?L -1 in vitro cultured cortical neurons. In the chronic injury model after 'reperfusion' melatonin (10 -6 , 10 -7 , 10 -8 mol?L -1 ) significantly decreased LDH activity and increased MTT value in neurons and glia co-cultured. But in the acute injury model, melatonin obviously increased LDH activity and decreased MTT value. CONCLUSION Melatonin protection for neuron from injuries induced by oxygen and glucose deprivation may be related to increase in the level of NO and decrease in the content of MDA. Melatonin can antagonize the injury in the chronic injury model after 'reperfusion', but exaggerate the injury in the acute injury model. These may be all related to its antioxidant action. Our results also suggest that melatonin may probably inhibit activation of microglia.