Slow-release and injected progesterone treatments enhance acute recovery after traumatic brain injury
Slow-release and injected progesterone treatments enhance acute recovery after traumatic brain injury
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DOI：
10.1016/j.pbb.2006.05.029
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发表时间：
2006-07-01
影响因子：
3.6
通讯作者：
Stein, Donald G.
中科院分区：
文献类型：
--
作者：
Cutler, Sarah M.;VanLandingham, Jacob W.;Stein, Donald G.
在创伤性脑损伤（TBI）大鼠模型中，通过皮下硅胶胶囊植入物持续释放孕酮与每日皮下注射孕酮的益处进行了比较。成年雄性Sprague-Dawley大鼠接受双侧额叶皮质挫伤或假手术。大鼠在损伤后1和6小时注射黄体酮或载体，然后每24小时注射一次，连续6天，在最后两次治疗中剂量逐渐减少。在动物麻醉的同时，在损伤后植入孕激素填充的硅胶胶囊。在tbi前后分别评估焦虑和运动活动的行为分析。脑损伤后8天提取脑，准备用于分子分析。与每日注射黄体酮的动物相比，服用胶囊的动物的焦虑行为减少，GABAA-4水平的降低也增加了焦虑行为的减少。与注射黄体酮组相比，所有植入胶囊组的运动活动都增加了。综上所述，TBI后稳定状态黄体酮治疗可减少水肿和焦虑，增加活动，从而促进行为恢复。在转化和临床试验中，连续的药理学给药模式可能比同一时间段内的大剂量注射更有益。(c) 2006爱思唯尔公司版权所有。
The benefits of continuous progesterone release via subcutaneous silastic capsule implants were compared to daily subcutaneous injections in a rat model of traumatic brain injury (TBI). Adult male Sprague-Dawley rats received either bilateral frontal cortex contusions or sham surgery. Rats were injected with progesterone or vehicle at I and 6 h post-injury, then once every 24 h for six days with tapering of the dose over the final two treatments. Progesterone-packed silastic capsules were implanted post-injury while the animals were anesthetized. Behavioral assays for anxiety and locomotor activity were evaluated pre- and post-TBI. Brains were extracted eight days post-TBI and prepared for molecular assays. Decreased GABAA-4 levels complemented a decrease in anxiety behaviors on the Elevated Plus Maze for capsule compared to progesterone-injected animals prior to daily injections. All groups with implanted capsules increased locomotor activity compared to those given progesterone injections. In conclusion, steady-state progesterone treatment after TBI decreases edema and anxiety and increases activity, thus enhancing behavioral recovery. A continuous mode of pharmacological administration may prove to be more beneficial in translational and clinical testing than bolus injections over the same period of time. (c) 2006 Elsevier Inc. All rights reserved.