Effects of progesterone administration on infarct volume and functional deficits following permanent focal cerebral ischemia in rats.

Effects of progesterone administration on infarct volume and functional deficits following permanent focal cerebral ischemia in rats.
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DOI:
10.1016/j.brainres.2008.12.048
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发表时间:
2009-02-27
期刊:
影响因子:
2.9
通讯作者:
Stein DG
Stein DG
中科院分区:
医学3区
文献类型:
--
作者:
Ishrat T;Sayeed I;Atif F;Stein DG

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最近的实验证据表明,孕激素(PROG)保护对各种模型的脑损伤,包括缺血性中风。尽管在动物模型上取得了初步的成功,但大多数急性脑卒中药物治疗的人类研究都失败了。为了更好地模拟无再灌注的典型人类中风,本研究使用直接烧灼大脑中动脉(MCA)来检查PROG对永久性中风模型中梗死体积和功能结局的功效。24只成年雄性Sprague-Dawley大鼠通过电凝和假手术进行pMCAO。在诱导永久性MCA闭塞(pMCAO)后,大鼠在闭塞后1h接受PROG(8 mg/kg)或载体的初始腹膜内注射,随后在6、24和48 h皮下注射。在pMCAO后24、48和72 h在旋转杆和握力计上测试功能缺陷。手术后72 h处死大鼠,将分离的脑切片成冠状切片并用2,3,5-氯化三苯基四氮唑(TTC)染色。与载体对照相比,PROG处理的大鼠显示梗死体积(%对侧半球)显著减少(54.05%)。此外,与媒介物相比,在用PROG处理的pMCAO大鼠中观察到保持在加速旋转棒上的能力显著改善和增加的握力。总之,这些数据表明,PROG是有益的中风的最佳表征模型之一,并可能保证在未来的人类中风的临床试验进一步测试。
Recent experimental evidence indicates that progesterone (PROG) protects against various models of brain injury, including ischemic stroke. Most human studies of pharmacologic treatments for acute cerebral stroke have failed despite initial success in animal models. To simulate better the typical human stroke without reperfusion, the present study was conducted to examine the efficacy of PROG on infarct volume and functional outcome in a permanent model of stroke, using direct cauterization of the middle cerebral artery (MCA). Twenty-four male adult Sprague-Dawley rats underwent pMCAO by electro-coagulation and sham operation. After induction of permanent MCA occlusion (pMCAO), the rats received an initial intraperitoneal injection of PROG (8 mg/kg) or vehicle at 1h post-occlusion followed by subcutaneous injections at 6, 24 and 48 h. Functional deficits were tested on the rotarod and grip strength meter at 24, 48 and 72 h after pMCAO. The rats were killed 72 h after surgery and isolated brain was sectioned into coronal slices and stained with 2, 3, 5-triphenyltetrazolium chloride (TTC). PROG-treated rats showed a substantial reduction (54.05%) in the volume of the infarct (% contralateral hemisphere) compared to vehicle controls. In addition there was a significant improvement in ability to remain on an accelerating rotarod and increased grip strength observed in the pMCAO rats treated with PROG compared to vehicle. Taken together, these data indicate that PROG is beneficial in one of the best-characterized models of stroke, and may warrant further testing in future clinical trials for human stroke.
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