Department of Emergency Medicine, Emory University, Atlanta, Georgia, United States of America.
PLoS One. 2014 Jan 28;9(1):e87252. doi: 10.1371/journal.pone.0087252. eCollection 2014.
Controlled cortical impact (CCI) models in adult and aged Sprague-Dawley (SD) rats have been used extensively to study medial prefrontal cortex (mPFC) injury and the effects of post-injury progesterone treatment, but the hormone's effects after traumatic brain injury (TBI) in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury.
Twenty-eight-day old (PND 28) male Sprague Dawley rats received sham (n = 24) or CCI (n = 47) injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight) or vehicle injections on post-injury days (PID) 1-7, subjected to behavioral testing from PID 9-27, and analyzed for lesion size at PID 28.
The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats.
Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits.
成年和老年 Sprague-Dawley(SD)大鼠的皮质控制冲击(CCI)模型已被广泛用于研究内侧前额叶皮质(mPFC)损伤和损伤后孕酮治疗的影响,但尚未确定创伤性脑损伤(TBI)后幼年动物中激素的作用。在本概念验证研究中,我们研究了孕酮在中度至重度双侧脑损伤的儿科模型中是否具有神经保护作用。
28 天大(PND 28)雄性 Sprague Dawley 大鼠接受假手术(n = 24)或 CCI(n = 47)损伤,并在损伤后第 1-7 天给予孕酮(4、8 或 16 mg/kg 每 100 g 体重)或载体注射,在 PND 9-27 进行行为测试,并在 PND 28 分析损伤大小。
观察到孕酮的 8 和 16 mg/kg 剂量最有利于减少 CCI 对 PND 28 雄性 SD 大鼠损伤大小和行为的影响。
我们的发现表明,中线 CCI 损伤额叶皮层将可靠地产生类似于成年雄性大鼠中所见的中度 TBI,并且孕酮可以改善损伤引起的缺陷。