RU486 Mitigates Hippocampal Pathology Following Status Epilepticus.
RU486 Mitigates Hippocampal Pathology Following Status Epilepticus.
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DOI：
10.3389/fneur.2016.00214
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发表时间：
2016
影响因子：
3.4
通讯作者：
Danzer SC
中科院分区：
文献类型：
--
作者：
Wulsin AC;Herman JP;Danzer SC
癫痫持续状态（SE）诱导下丘脑-垂体-肾上腺皮质（HPA）轴的快速超激活。下丘脑轴过度活跃导致过量暴露于高水平的循环糖皮质激素，这与神经毒性和抑郁样行为有关。这些观察结果导致了下丘脑轴功能障碍可能加剧se诱导的脑损伤的假设。为了验证这一假设，我们使用小鼠癫痫模型来确定使用糖皮质激素受体拮抗剂RU486是否可以减轻SE后的海马病理。小鼠在SE发作1天后明显出现糖皮质激素分泌过量，随后出现自发性癫痫发作（可能需要数周时间）。RU486处理阻断了匹罗卡品处理小鼠糖皮质激素水平se相关升高。RU486治疗还可以减轻SE诱导的海马病变的发展，减少门状苔藓细胞的损失，限制齿状门的病理细胞增殖。苔藓细胞的丢失和异位肝门细胞的积累与癫痫的严重程度正相关，提示早期使用糖皮质激素拮抗剂治疗可能具有抗癫痫作用。
Status epilepticus (SE) induces rapid hyper-activation of the hypothalamo–pituitary–adrenocortical (HPA) axis. HPA axis hyperactivity results in excess exposure to high levels of circulating glucocorticoids, which are associated with neurotoxicity and depression-like behavior. These observations have led to the hypothesis that HPA axis dysfunction may exacerbate SE-induced brain injury. To test this hypothesis, we used the mouse pilocarpine model of epilepsy to determine whether use of the glucocorticoid receptor antagonist RU486 can attenuate hippocampal pathology following SE. Excess glucocorticoid secretion was evident 1 day after SE in the mice, preceding the development of spontaneous seizures (which can take weeks to develop). RU486 treatment blocked the SE-associated elevation of glucocorticoid levels in pilocarpine-treated mice. RU486 treatment also mitigated the development of hippocampal pathologies induced by SE, reducing loss of hilar mossy cells and limiting pathological cell proliferation in the dentate hilus. Mossy cell loss and accumulation of ectopic hilar cells are positively correlated with epilepsy severity, suggesting that early treatment with glucocorticoid antagonists could have anti-epileptogenic effects.
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实验性颞叶癫痫中血浆皮质酮水平升高和抑郁行为。
影响因子：
6.1
作者：
Mazarati AM;Shin D;Kwon YS;Bragin A;Pineda E;Tio D;Taylor AN;Sankar R
通讯作者：
Sankar R
影响因子：
3.7
作者：
Castro OW;Santos VR;Pun RY;McKlveen JM;Batie M;Holland KD;Gardner M;Garcia-Cairasco N;Herman JP;Danzer SC
通讯作者：
Danzer SC
DOI：
10.1016/0960-0760(90)90489-8
发表时间：
1990-11-20
影响因子：
4.1
作者：
DEKLOET, ER;REUL, JMHM;SUTANTO, W
通讯作者：
SUTANTO, W
影响因子：
3.3
作者：
McCullers, D;Sullivan, PG;Herman, JP
通讯作者：
Herman, JP
DOI：
10.3969/j.issn.1672-7347.2011.11.007
发表时间：
2011-11-01
期刊：
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences
影响因子：
--
作者：
Liu, Jianxin;Tang, Fengru;Liu, Yong
通讯作者：
Liu, Yong