Unidad de Investigación Médica en Farmacología, Centro Médico Nacional Siglo XXI, IMSS, México DF, México.
Restor Neurol Neurosci. 2011;29(1):1-15. doi: 10.3233/RNN-2011-0571.
To assess the longterm neuroprotective effects of progesterone (P₄) and allopregnanolone (ALLO) on functional and morphological parameters of the integrity of the hippocampus, after global cerebral ischemia.
Adult male Sprague-Dawley rats were subjected to a transient severe (20 min) forebrain ischemia (Isch) episode and treated with P₄ or ALLO (8 mg/kg i.v.) or its vehicle, at 20 min, 2, 6, 24, 48 and 72 h after ischemia. Rats subjected to Sham procedures, and intact rats were included as nonischemic controls. Three months after ischemia, both the functional (spatial learning and memory, and reference and working memory), and the morphological integrity (dimensions of the hippocampal formation, thickness of the CA1 subfield, and pyramidal neuron population) of the hippocampus and the medial prefrontal cortex(mPFC) were determined.
Treatment with P₄ or ALLO significantly reduced the impairment in spatial learning and memory, as well as in reference and working memory, and prevented the narrowing of the hippocampus, otherwise induced by ischemia. This better performance of P₄ and ALLO treated rats than vehicle (Veh) treated rats, occurred in spite of a loss of pyramidal neurons in the CA1, CA2,CA3 and hilus subfields of the Ammon's horn (remaining neurons: Isch+Veh: 21.0, 35.6, 44.1, and 40.3%; Isch+P₄: 19.9, 32.2,41.1, and 32.5%; Isch+ALLO: 25.5, 62.0, 73.7, and 56.7%), and nonsignificant changes in the mPFC, as compared to the Intact group (100%).
Performance of P₄ or ALLO treated rats in learning and memory tests suggests that these steroids promoted neural conditions accounting for adequate functioning long after ischemia, in spite of the loss of hippocampal pyramidal neurons.
评估孕酮（P₄）和别孕烯醇酮（ALLO）对全脑缺血后海马功能和形态完整性的长期神经保护作用。
成年雄性 Sprague-Dawley 大鼠接受短暂严重（20 分钟）前脑缺血（Isch）发作，并在缺血后 20 分钟、2 小时、6 小时、24 小时、48 小时和 72 小时用 P₄ 或 ALLO（8mg/kg 静脉注射）或其载体治疗。假手术和完整大鼠作为非缺血对照。缺血后 3 个月，评估海马和内侧前额叶皮质（mPFC）的功能（空间学习和记忆以及参考和工作记忆）和形态完整性（海马结构的维度、CA1 亚区的厚度和锥体神经元群体）。
用 P₄ 或 ALLO 治疗可显著减轻空间学习和记忆以及参考和工作记忆的损伤，并防止海马因缺血引起的变窄。与 Veh 治疗组相比，P₄ 和 ALLO 治疗组的表现更好，尽管 Ammon 角的 CA1、CA2、CA3 和齿状回亚区的锥体神经元丢失（剩余神经元：Isch+Veh：21.0、35.6、44.1 和 40.3%；Isch+P₄：19.9、32.2、41.1 和 32.5%；Isch+ALLO：25.5、62.0、73.7 和 56.7%），而 mPFC 无明显变化，与完整组（100%）相比。
P₄ 或 ALLO 治疗组在学习和记忆测试中的表现表明，这些类固醇在缺血后很长时间内促进了神经状态，尽管海马锥体神经元丢失，但仍能维持适当的功能。
