[Effects of edaravone, minocycline and ONO-1078 on oxygen/glucose deprivation-induced electrophysiological alteration in rat hippocampal slices].
OBJECTIVE
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].


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Li
Wei
W
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310031, China. weieq2001@yahoo.com
Wei
Er-qing
EQ
Wang
Meng-ling
ML
Liu
Lu-ying
LY
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002545:Brain Ischemia / Q000503:physiopathology; D002867:Chromones / Q000494:pharmacology*; D000077553:Edaravone; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D020024:Leukotriene Antagonists / Q000494:pharmacology; D008911:Minocycline / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D002867:Chromones; D016166:Free Radical Scavengers; D020024:Leukotriene Antagonists; D018696:Neuroprotective Agents; D008911:Minocycline; D005947:Glucose; D000077553:Edaravone; D000983:Antipyrine; C047681:pranlukast