Characterizing a mouse model for evaluation of countermeasures against hydrogen sulfide-induced neurotoxicity and neurological sequelae.
Characterizing a mouse model for evaluation of countermeasures against hydrogen sulfide-induced neurotoxicity and neurological sequelae.
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DOI：
10.1111/nyas.13419
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发表时间：
2017-07
影响因子：
5.2
通讯作者：
Rumbeiha WK
中科院分区：
文献类型：
--
作者：
Anantharam P;Whitley EM;Mahama B;Kim DS;Imerman PM;Shao D;Langley MR;Kanthasamy A;Rumbeiha WK
硫化氢（H2S）是一种高度神经毒性气体。这是第二个最常见的原因气体引起的死亡。除了死亡，急性暴露的幸存受害者可能会遭受长期的神经后遗症。有必要制定预防H2S中毒的对策。然而，不存在H2S诱导的神经系统后遗症的转化动物模型。在这里，我们描述了一种新的小鼠模型H2S诱导的神经毒性的转化研究。在范例I中，C57/BL 6小鼠在第1天暴露于765 ppm H2S 40分钟，随后每天暴露15分钟，持续1至6天。在范例II中，将小鼠暴露于1000 ppm H2S一次，持续60分钟。评估小鼠的行为、神经化学、生物化学和组织病理学变化。H2S中毒引起癫痫发作、呼吸困难、呼吸抑制、击倒和死亡。与对照组相比，H2S暴露的小鼠在运动和协调运动活动中表现出显著的损伤。组织学检查显示丘、丘脑和皮质脑区域的神经退行性病变。硫化氢显着增加多巴胺和5-羟色胺浓度在几个脑区，并导致GABA和谷氨酸浓度的时间依赖性下降。此外，H2S显着抑制细胞色素c氧化酶的活性，并造成显着的损失，体重。总体而言，雄性小鼠比雌性小鼠更敏感。这种新的翻译H2S诱导的神经毒性小鼠模型是可靠的，可重复的，并概括了人类急性H2S中毒。
Hydrogen sulfide (H2S) is a highly neurotoxic gas. It is the second most common cause of gas-induced deaths. Beyond mortality, surviving victims of acute exposure may suffer long-term neurological sequelae. There is a need to develop countermeasures against H2S poisoning. However, no translational animal model of H2S-induced neurological sequelae exists. Here, we describe a novel mouse model of H2S-induced neurotoxicity for translational research. In paradigm I, C57/BL6 mice were exposed to 765 ppm H2S for 40 min on day 1, followed by 15-min daily exposures for periods ranging from 1 to 6 days. In paradigm II, mice were exposed once to 1000 ppm H2S for 60 minutes. Mice were assessed for behavioral, neurochemical, biochemical, and histopathological changes. H2S intoxication caused seizures, dyspnea, respiratory depression, knockdowns, and death. H2S-exposed mice showed significant impairment in locomotor and coordinated motor movement activity compared with controls. Histopathology revealed neurodegenerative lesions in the collicular, thalamic, and cortical brain regions. H2S significantly increased dopamine and serotonin concentration in several brain regions and caused time-dependent decreases in GABA and glutamate concentrations. Furthermore, H2S significantly suppressed cytochrome c oxidase activity and caused significant loss in body weight. Overall, male mice were more sensitive than females. This novel translational mouse model of H2S-induced neurotoxicity is reliable, reproducible, and recapitulates acute H2S poisoning in humans.
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影响因子：
3.1
作者：
Groenewegen HJ
通讯作者：
Groenewegen HJ
DOI：
10.3109/15563650.2014.990976
发表时间：
2015-01
期刊：
Clinical toxicology (Philadelphia, Pa.)
影响因子：
--
作者：
Haouzi P;Chenuel B;Sonobe T
通讯作者：
Sonobe T
影响因子：
1.6
作者：
Doujaiji, Bassam;Al-Tawfiq, Jaffar A.
通讯作者：
Al-Tawfiq, Jaffar A.
影响因子：
4.7
作者：
Gadalla MM;Snyder SH
通讯作者：
Snyder SH
影响因子：
5.1
作者：
Guidotti, TL
通讯作者：
Guidotti, TL