Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People's Republic of China.
Behav Brain Res. 2010 May 1;209(1):119-22. doi: 10.1016/j.bbr.2010.01.026. Epub 2010 Jan 28.
Recent studies indicate that progesterone (PROG) protects against animal brain injury, including ischemic stroke, in various animal models. However, there are insufficient studies about PROG in other various groups such as ovariectomized females and aged animals. This study was designed to examine the efficacy of PROG on infarct volume, brain water content and functional outcome after cerebral ischemia in aged rats. Thirty-six male aged Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO) with the intraluminal filament technique and sham operation. After induction of pMCAO, the rats received an initial intraperitoneal injection of PROG (8mg/kg) or vehicle at 1h post-occlusion followed by subcutaneous injections at 6, 24 and 48h. Functional deficits were tested with Zea Longa and Rotarod test at 24, 48 and 72h after pMCAO. The rats were killed 72h after surgery and infarct volume were determined with 2,3,5-triphenyltetrazolium chloride (TTC) staining and digital image analysis. Brain water content was determined by the dry-wet weight method. PROG-treated rats showed a substantial reduction in the volume of the infarction (% contralateral hemisphere) and brain water content compared to vehicle-treated rats. In addition, there was a significant improvement in ability to remain on an accelerating rotarod and increased Zea Longa scores observed in the pMCAO rats treated with PROG compared to vehicle. These findings point to the response of aged adult rats to PROG in cerebral ischemia, and suggest that such response need to be considered in the development of neuroprotective agents for stroke.
最近的研究表明，孕酮（PROG）在各种动物模型中可预防动物脑损伤，包括缺血性中风。然而，关于 PROG 在其他各种群体（如去卵巢雌性动物和老年动物）中的研究还不够充分。本研究旨在研究 PROG 对老年大鼠脑缺血后梗死体积、脑水含量和功能结果的疗效。36 只雄性老年 Sprague-Dawley 大鼠通过腔内纤维丝技术进行永久性大脑中动脉闭塞（pMCAO）和假手术。pMCAO 诱导后，大鼠在闭塞后 1 小时接受 PROG（8mg/kg）或载体的初始腹腔注射，随后在 6、24 和 48 小时进行皮下注射。pMCAO 后 24、48 和 72 小时，通过 Zea Longa 和转棒试验测试功能缺陷。手术后 72 小时，大鼠被处死，通过 2,3,5-三苯基氯化四氮唑（TTC）染色和数字图像分析测定梗死体积。通过干重-湿重法测定脑水含量。与载体处理的大鼠相比，PROG 处理的大鼠梗死体积（对侧半球的%）和脑水含量显著减少。此外，与载体处理的大鼠相比，PROG 处理的 pMCAO 大鼠在加速转棒上保持能力的能力显著提高，Zea Longa 评分也增加。这些发现表明，老年成年大鼠对 PROG 在脑缺血中的反应，并且表明在开发用于中风的神经保护剂时需要考虑这种反应。
