Mifepristone protects CA1 hippocampal neurons following traumatic brain injury in rat
Mifepristone protects CA1 hippocampal neurons following traumatic brain injury in rat
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DOI：
10.1016/s0306-4522(01)00477-8
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发表时间：
2002-01-01
期刊：
影响因子：
3.3
通讯作者：
Herman, JP
中科院分区：
文献类型：
--
作者：
McCullers, D;Sullivan, PG;Herman, JP
本研究探讨了微皮质激素受体和糖皮质激素受体对实验性创伤性脑损伤后海马神经元活力的影响。大鼠分别用载体、矿皮质激素受体拮抗剂螺内酯或糖皮质激素受体拮抗剂米非司酮（RU486）预处理48 h，然后进行假手术或单侧控制性皮质撞击损伤。为了确定受体拮抗剂预处理对细胞存活的影响，在损伤后24 h，采用光学分划法对海马CA1、CA3和齿状回区域的神经元进行计数。损伤减少了载药预处理动物CA1和CA3活性神经元的数量。值得注意的是，RU486预处理可以防止CA1细胞的这种损失。在齿状回中也观察到神经元丢失。通过原位杂交分析，比较bel-2、bax和p53信使RNA的相对水平，评估受体阻断和损伤对存活率相关基因表达的影响。螺内酯和RU486降低了CA1和齿状回的基础bel-2信使RNA水平，但不影响基础bax或p53水平。损伤降低了齿状回bel-2信使RNA水平，但不影响载具预处理动物的bax或p53水平。这些数据表明，RU486预处理可防止外伤性脑损伤后CA1锥体神经元24it的丢失。RU486对bel-2、bux或p53信使RNA表达的调节并不能预测此时神经元的活力，这表明RU486介导的CA1神经元的保存与这些细胞死亡相关基因的转录调节无关。(c) 2002年ibro。Elsevier Science Ltd.出版。版权所有。
The present study addresses mincralocorticoid receptor and glucocorticoid receptor effects on hippocampal neuron viability after experimental traumatic brain injury. Rats were pretreated for 48 h with vehicle, the mineralocorticoid receptor antagonist spironolactone, or the glucocorticoid receptor antagonist mifepristone (RU486) and subsequently subjected to sham operation or unilateral controlled cortical impact injury. To determine the effects of receptor antagonist pretreatments on cell survival, neurons in regions CA1, CA3, and dentate gyrus of the hippocampal formation were counted 24 h post-injury using the optical fractionator method. Injury decreased the number of viable neurons in CA1 and CA3 of vehicle-pretreated animals. Notably, this cell loss was prevented in CA1 by RU486 pretreatment. Neuronal loss was also observed in dentate gyros. The effects of receptor blockade and injury on the expression of viability-related genes were also assessed by comparing relative bel-2, bax, and p53 messenger RNA levels using in situ hybridization analysis. Spironolactone and RU486 decreased basal bel-2 messenger RNA levels in CA1 and dentate gyrus but did not affect basal bax or p53 levels. Injury decreased bel-2 messenger RNA levels in dentate gyrus but did not affect bax or p53 levels in vehicle-pretreated animals.These data demonstrate that RU486 pretreatment prevents the loss of CA1 pyramidal neurons 24 It after traumatic brain injury. RU486 modulation of bel-2, bux, or p53 messenger RNA expression does not predict neuronal viability at this time point, suggesting that RU486-mediated preservation of CA1 neurons does not involve transcriptional regulation of those cell death-related genes. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.