Peterson Bethany L, Won Soonmi, Geddes Rastafa I, Sayeed Iqbal, Stein Donald G
Department of Emergency Medicine, Emory University, Atlanta, GA 30322, USA.
Department of Emergency Medicine, Emory University, Atlanta, GA 30322, USA.
Behav Brain Res. 2015 Jun 1;286:152-65. doi: 10.1016/j.bbr.2015.03.005. Epub 2015 Mar 6.
There is no satisfactory therapeutic intervention for neonatal hypoxic-ischemic (HI) encephalopathy. Progesterone is known to be effective in treating traumatic brain injury in adult animals but its effects in neonatal brains have not been reported. Brain injuries were induced by a unilateral common carotid artery ligation plus hypoxia exposure. Progesterone was administered immediately after hypoxia and daily for 5 days at 8 mg/kg, followed by a tapered dose for two days. At six weeks post-injury, lesion size and inflammatory factors were evaluated. Progesterone-treated, HI-injured male animals, but not females, showed significant long-term tissue protection compared to vehicle, suggesting an important sex difference in neuroprotection. Progesterone-treated, HI-injured male rats had fewer activated microglia in the cortex and hippocampus compared to controls. The rats were tested for neurological reflexes, motor asymmetry, and cognitive performance at multiple time points. The injured animals exhibited few detectable motor deficits, suggesting a high level of age- and injury-related neuroplasticity. There were substantial sex differences on several behavioral tests, indicating that immature males and females should be analyzed separately. Progesterone-treated animals showed modest beneficial effects in both sexes compared to vehicle-treated injured animals. Sham animals given progesterone did not behave differently from vehicle-treated sham animals on any measures.
对于新生儿缺氧缺血性（HI）脑病，目前尚无令人满意的治疗干预措施。已知孕酮对成年动物的创伤性脑损伤有效，但尚未有其对新生儿脑作用的报道。通过单侧颈总动脉结扎加缺氧暴露诱导脑损伤。缺氧后立即给予孕酮，剂量为8mg/kg，每日1次，共5天，随后两天逐渐减量。在损伤后6周，评估损伤大小和炎症因子。与溶剂对照组相比，接受孕酮治疗的HI损伤雄性动物（而非雌性动物）显示出显著的长期组织保护作用，提示神经保护存在重要的性别差异。与对照组相比，接受孕酮治疗的HI损伤雄性大鼠在皮质和海马中活化的小胶质细胞较少。在多个时间点对大鼠进行神经反射、运动不对称性和认知能力测试。损伤动物几乎没有可检测到的运动缺陷，表明与年龄和损伤相关的神经可塑性水平较高。在多项行为测试中存在显著的性别差异，表明未成熟的雄性和雌性应分别进行分析。与接受溶剂治疗的损伤动物相比，接受孕酮治疗的动物在两性中均显示出适度的有益效果。接受孕酮治疗的假手术动物在任何测量指标上与接受溶剂治疗的假手术动物表现无异。
