[Homeostatic conditions affect the protective effect of edaravone on ischemic injury in neurons]
1Department of Pharmacology, College of Medicine, Zhejiang University, Hangzhou 310031, China.
Objective:
To determine whether homeostatic conditions (pH, glycine or ion concentration) affect the protective effects of edaravone on ischemic injury in rat cortical neurons.
Methods:
In cultured rat cortical neurons, the compositions in the experimental solutions were changed to mimic the disturbance of homeostasis after cerebral ischemia. In vitro ischemic injury was induced by oxygen-glucose deprivation (OGD) for 3 h and reperfusion for 12 h, and the neuron injury was evaluated by 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium bromide (MTT) reduction assay and lactate dehydrogenase (LDH) release. Effect of edaravone on OGD injury was observed in different experimental solutions.
Result:
In weak alkalified solution (pH 7.8) or the solution containing glycine (10 micromol/L), OGD injury became more serious; but in weak acidic (pH 6.5) or higher Mg(2+) (1.8 mmol/L) solutions, OGD injury was attenuated. Edaravone (1 micromol/L) reversed the injury in the solutions with pH 6.1,7.4 and 7.8 or the solution containing glycine, but did not show protective effect in the solution with pH 6.5 and the higher Mg(2+) or lower Ca(2+) solution.
Conclusion:
The changes of homeostatic conditions affect the severity of ischemic injury of neurons and the protective effect of edaravone.
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