Department Section of Vascular Neurology, Heart Center, Semmelweis University, Gaál J. Street 9-11, 1122, Budapest, Hungary.
Behav Brain Res. 2010 May 1;209(1):42-8. doi: 10.1016/j.bbr.2010.01.010. Epub 2010 Jan 18.
Although much is known about the protective effect of acute estrogen therapy in cerebral ischemia, relatively little is known about its effect on functional outcome at different ages. The impact of age is, however, important on the efficacy of steroids in the central nervous system. We investigated whether a single dose of estradiol pre-treatment would be neuroprotective in young (4 months), middle-aged (9 months) and old (18 months) female gerbils following 10min global brain ischemia. Apoptotic and necrotic cells were labelled and quantified in the affected hippocampus; exploratory activity, attention and memory functions were tested using open field, spontaneous alternation, novel object recognition and hole-board test. Age effect and treatment effect were analysed. High single dose (4mg/kg b.w.) of estradiol pre-treatment exposed a marked neuroprotective effect against hippocampal cell loss in all age groups. In behavioural tests, however, age-related differences could be observed. In middle-aged and old animals the worsening in memory function following ischemia was more prominent compared to that in the young ones. In the Y-maze and the novel object recognition tests the middle-aged, in the hole-board test (investigating working memory and total time) the old gerbils had the worst functional outcome. Only reference memory in hole-board test did not change by age. Estrogen improved memory performances in all the tests at every age. We can conclude that age of experimental animals is a factor worsening the outcome following brain ischemia. A single-dose estrogen therapy prevents the lesion-induced behavioural dysfunctions and the hippocampal cell loss.
尽管人们对急性雌激素治疗在脑缺血中的保护作用有了很多了解，但对其在不同年龄阶段对功能结果的影响却知之甚少。然而，年龄对类固醇在中枢神经系统中的疗效有重要影响。我们研究了在 10 分钟全脑缺血后，单次给予雌二醇预处理是否对年轻（4 个月）、中年（9 个月）和老年（18 个月）雌性沙鼠具有神经保护作用。用凋亡和坏死细胞标记物并在受影响的海马体中进行定量；使用旷场、自发交替、新物体识别和洞板测试来测试探索性活动、注意力和记忆功能。分析年龄效应和治疗效果。高剂量（4mg/kg b.w.）的雌二醇预处理对所有年龄组的海马体细胞丢失均表现出明显的神经保护作用。然而，在行为测试中，可以观察到与年龄相关的差异。在中年和老年动物中，与年轻动物相比，缺血后记忆功能的恶化更为明显。在 Y 迷宫和新物体识别测试中，中年动物，在洞板测试（研究工作记忆和总时间）中，老年沙鼠的功能结果最差。只有参考记忆在洞板测试中不受年龄变化的影响。雌激素改善了所有测试中的记忆表现。我们可以得出结论，实验动物的年龄是影响脑缺血后结果的一个因素。单次雌激素治疗可预防损伤引起的行为功能障碍和海马体细胞丢失。
