Post-exposure administration of diazepam combined with soluble epoxide hydrolase inhibition stops seizures and modulates neuroinflammation in a murine model of acute TETS intoxication.
Post-exposure administration of diazepam combined with soluble epoxide hydrolase inhibition stops seizures and modulates neuroinflammation in a murine model of acute TETS intoxication.
复制标题
地西ep剂的暴露后给药结合可溶性环氧化物水解酶抑制作用，可停止癫痫发作，并在急性TET中毒的鼠模型中调节神经炎症。
DOI：
10.1016/j.taap.2014.10.001
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发表时间：
2014-12-01
影响因子：
3.8
通讯作者：
Lein, Pamela J.
中科院分区：
文献类型：
--
作者：
Vito, Stephen T.;Austin, Adam T.;Banks, Christopher N.;Inceoglu, Bora;Bruun, Donald A.;Zolkowska, Dorota;Tancredi, Daniel J.;Rogawski, Michael A.;Hammock, Bruce D.;Lein, Pamela J.
关键词：
Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABAAR) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABAAR positive allosteric modulator, on seizure activity, death and neuroinflammation in adult male Swiss mice injected with a lethal dose of TETS (0.15 mg/kg, ip). Administration of a high dose of diazepam (5 mg/kg, ip) immediately following the second clonic seizure (approximately 20 min post-TETS injection) effectively prevented progression to tonic seizures and death. However, this treatment did not prevent persistent reactive astrogliosis and microglial activation, as determined by GFAP and Iba-1 immunoreactivity and microglial cell morphology. Inhibition of soluble epoxide hydrolase (sEH) has been shown to exert potent anti-inflammatory effects and to increase survival in mice intoxicated with other GABAAR antagonists. The sEH inhibitor TUPS (1 mg/kg, ip) administered immediately after the second clonic seizure did not protect TETS-intoxicated animals from tonic seizures or death. Combined administration of diazepam (5 mg/kg, ip) and TUPS (1 mg/kg, ip, starting 1 h after diazepam and repeated every 24 h) prevented TETS-induced lethality and influenced signs of neuroinflammation in some brain regions. Significantly decreased microglial activation and enhanced reactive astrogliosis were observed in the hippocampus, with no changes in the cortex. Combining an agent that targets specific anti-inflammatory mechanisms with a traditional antiseizure drug may enhance treatment outcome in TETS intoxication.
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影响因子：
13.5
作者：
Harry, G. Jean
通讯作者：
Harry, G. Jean
影响因子：
2.5
作者：
MATTHEWS, MA;KRUGER, L
通讯作者：
KRUGER, L
DOI：
10.1081/clt-120026523
发表时间：
2003-01-01
期刊：
JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY
影响因子：
--
作者：
Barrueto, F;Furdyna, PM;Nelson, LS
通讯作者：
Nelson, LS
影响因子：
3.7
作者：
Inceoglu B;Zolkowska D;Yoo HJ;Wagner KM;Yang J;Hackett E;Hwang SH;Lee KS;Rogawski MA;Morisseau C;Hammock BD
通讯作者：
Hammock BD
影响因子：
4.7
作者：
Drexel M;Preidt AP;Sperk G
通讯作者：
Sperk G