Postinjury administration of 17β-estradiol induces protection in the gray and white matter with associated functional recovery after cervical spinal cord injury in male rats.
Postinjury administration of 17β-estradiol induces protection in the gray and white matter with associated functional recovery after cervical spinal cord injury in male rats.
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DOI：
10.1002/cne.23056
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发表时间：
2012-08-15
期刊：
影响因子：
--
通讯作者：
Floyd CL
中科院分区：
文献类型：
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作者：
Siriphorn A;Dunham KA;Chompoopong S;Floyd CL
诊所中的大多数脊髓损伤（SCI）发生在较低的颈部水平，导致白色和灰质破坏。相比之下，大多数啮齿动物SCI实验模型诱导胸髓损伤，主要导致白色物质破坏。为了解决这一差异，已经开发了实验性颈脊髓损伤模型。因此，我们使用最近表征的成年雄性大鼠颈部半挫伤SCI模型来评估SCI后给予17β-雌二醇的潜在治疗效果。大鼠在第五颈椎（C5）水平接受半挫伤，然后在SCI后30分钟开始通过缓释丸（0.5或5.0 mg/丸）给予17β-雌二醇。脊髓损伤后7周，对熟练和非熟练前肢功能和运动功能进行行为学评价。在行为评估结束后，收集脊髓并进行组织化学和体视学，以评价给药对病变特征的影响。我们发现，SCI后给予17β-雌二醇可减少腹角神经元丢失，减少反应性星形胶质细胞增生，降低免疫反应，并增加损伤中心的白色白质保留。此外，SCI后给予17β-雌二醇改善了熟练的前肢功能和运动功能。综上所述，这些数据表明，脊髓损伤后给予17β-雌二醇可保护脊髓颈段灰质和白色物质。此外，这种治疗改善了涉及灰质和白色物质成分的熟练运动任务的功能，表明这可能是一种高度临床相关的保护策略。
The majority of spinal cord injuries (SCIs) in the clinic occur at the lower cervical levels, resulting in both white and gray matter disruption. In contrast, most experimental models of SCI in rodents induce damage in the thoracic cord, resulting primarily in white matter disruption. To address this disparity, experimental cervical SCI models have been developed. Thus, we used a recently characterized model of cervical hemicontusion SCI in adult male rats to assess the potential therapeutic effect of post-SCI administration of 17β-estradiol. Rats received a hemicontusion at the level of the fifth cervical vertebra (C5) followed by administration of 17β-estradiol via a slow release pellet (0.5 or 5.0 mg/pellet) beginning at 30 minutes post-SCI. Behavioral evaluation of skilled and unskilled forelimb function and locomotor function were conducted for 7 weeks after SCI. Upon conclusion of the behavioral assessments, spinal cords were collected and histochemistry and stereology were conducted to evaluate the effect of treatment on the lesion characteristics. We found that post-SCI administration of 17β-estradiol decreased neuronal loss in the ventral horn, decreased reactive astrogliosis, decreased the immune response, and increased white mater sparing at the lesion epicenter. Additionally, post-SCI administration of 17β-estradiol improved skilled forelimb function and locomotor function. Taken together, these data suggest that post-SCI administration of 17β-estradiol protected both the gray and white matter in cervical SCI. Moreover, this treatment improved function on skilled motor tasks that involve both gray and white matter components, suggesting that this is likely a highly clinically relevant protective strategy.