Effects of edaravone, minocycline and ONO-1078 on oxygen/glucose deprivation-induced electrophysiological alteration in rat hippocampal slices / 药学学报

ABSTRACT

<p><b>AIM</b>To establish an in vitro model of hippocampal slice to detect electrophysiological alteration after oxygen/glucose deprivation (OGD), and to observe the effects of edaravone, minocycline and ONO-1078 [pranlukast, 4-oxo-8-[p-(4-phenylbutyloxy) benzoyl-amino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate].</p><p><b>METHODS</b>Hippocampal slices from rats were perfused with artificial cerebrospinal fluid lacking oxygen and glucose for 3, 4, 7 and 10 min. The population spike (PS) was recorded, and 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed in some experiments, to detect the slice viability in the presence or absence of drugs in the perfusion solution.</p><p><b>RESULTS</b>Four min of OGD treatment was the most suitable duration for induction of slice injury, and PS amplitudes were recovered to (29 +/- 6)% of baseline values within 1 h after 4 min OGD. Edaravone, a free radical scavenger, at 1 and 10 mumol.L-1 significantly increased the recovery rate to (56 +/- 13)% and (69 +/- 12)% of baseline respectively 1 h after OGD. However, the anti-inflammatory drug minocycline (10 mumol.L-1) and leukotriene receptor antagonist ONO-1078 (1 mumol.L-1) did not increase the recovery. NMDA receptor antagonist ketamine, as a positive control, also promoted the recovery concentration-dependently.</p><p><b>CONCLUSION</b>OGD for 4 min was a feasible in vitro ischemia model for determination on electrophysiological alteration in hippocampal slices. Edaravone showed concentration-dependent protective effect on OGD injury, and anti-inflammatory drugs minocycline and ONO-1078 showed no effect.</p>