Ovarian steroid modulation of seizure severity and hippocampal cell death after kainic acid treatment
Ovarian steroid modulation of seizure severity and hippocampal cell death after kainic acid treatment
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DOI：
10.1016/s0014-4886(03)00104-3
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发表时间：
2003-07-01
影响因子：
5.3
通讯作者：
Murphy, AZ
中科院分区：
文献类型：
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作者：
Hoffman, GE;Moore, N;Murphy, AZ
为了确定维持雌激素或孕激素水平是否影响kainic酸（KA）发作模式或海马神经元对癫痫发作死亡的敏感性，切除卵巢的Sprague-Dawley大鼠植入雌激素颗粒，0.1或0.5 mg，血清水平为42.4 +/- 6.6（平均+/- SEM）和242.4 +/- 32.6 pg/ml，或1至6粒孕激素胶囊，血清水平为11.00 +/- 0.72至48.62 +/- 9.4 ng/ml。7天后给予大鼠KA (8.5 mg/kg, ip)，并对癫痫发作活动进行评分；随后，将这些大鼠处死，处理它们的大脑以定位神经元核抗原（NeuN），这是一种通用的神经元标志物。对海马体的扩散（显示细胞损失的独立区域的数量）进行评分，并测量NeuN免疫反应性占据的CA野区内的面积（表明存活的神经元）。给予雌激素或黄体酮（与剂量无关）可显著降低KA发作的死亡率。黄体酮降低了接受一到四次植入的动物癫痫发作的严重程度；与对照组相比，植入六种黄体酮的动物癫痫发作的严重程度没有差异。服用黄体酮的动物癫痫发作减少的同时，海马损伤的扩散也减少(r(2) = 0.87；P < 0.05)。同样，在黄体酮治疗的大鼠中，神经元存活与癫痫发作评分降低相关(r(2) = 0.76；P < 0.0001)。雌激素对癫痫发作的严重程度无影响（P < 0.05），但可减少弥散性（P < 0.05）和神经元丢失程度（P < 0.05）。事实上，在雌激素治疗的大鼠中，神经元死亡明显低于同样严重癫痫发作的黄体酮治疗的大鼠（P < 0.05）。这些数据与黄体酮通过减少癫痫发作产生作用的假设是一致的，而雌激素对癫痫发作行为几乎没有有益的影响，但可以保护海马体免受癫痫发作造成的损害。(C) 2003 Elsevier Science（美国）版权所有。
To determine whether maintained estrogen or progesterone levels affect kainic acid (KA) seizure patterns or the susceptibility of hippocampal neurons to death from seizures, ovariectomized Sprague-Dawley rats were implanted with estrogen pellets, 0.1 or 0.5 mg, that generated serum levels of 42.4 +/- 6.6 (mean +/- SEM) and 242.4 +/- 32.6 pg/ml or one to six capsules of progesterone that generated serum levels of 11.00 +/- .72 to 48.62 +/- 9.4 ng/ml. Seven days later, the rats were administered KA (8.5 mg/kg, ip) and scored for seizure activity; 96 It later, the rats were killed and their brains processed for localization of neuron nuclear antigen (NeuN), a general neuronal marker. The hippocampus was scored for spread (the number of separate regions showing cell loss), and the area within the CA fields occupied by NeuN immunoreactivity was measured (indicating surviving neurons). Administration of estrogen or progesterone (independent of dose) significantly reduced mortality from KA seizures. Progesterone reduced seizure severity in animals that received one to four implants; compared with controls, no difference in seizure severity was noted for animals with six progesterone implants. The reduced seizures in progesterome-treated animals were accompanied by a reduction in the spread of hippocampal damage (r(2) = 0.87; P < 0.05). Likewise, in progesterone-treated rats, neuron survival and reduction in seizure scores were correlated (r(2) = 0.76; P < 0.0001). Estrogen had no effect on seizure severity (P > 0.05), but reduced both the spread (P < 0.05) and degree of neuronal loss (P < 0.05). Indeed, in the estrogen-treated rats, neuronal death was significantly lower than that observed in progesterone-treated animals with equally severe seizures (P < 0.05). These data are consistent with the hypothesis that progesterone produces its effects by reducing seizures, whereas estrogen has little beneficial effect on seizure behavior but protects the hippocampus from the damage seizures produce. (C) 2003 Elsevier Science (USA). All rights reserved.