Neuroprotective effects of estrogen in CNS injuries: insights from animal models.
Neuroprotective effects of estrogen in CNS injuries: insights from animal models.
复制标题
雌激素在中枢神经系统损伤中的神经保护作用：动物模型的见解。
DOI：
10.2147/nan.s105134
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Ray SK
中科院分区：
文献类型：
--
作者：
Raghava N;Das BC;Ray SK
在人体内生物合成的雌激素中，17β-雌二醇（雌二醇或E2）是中枢神经系统（CNS）损伤（如脊髓损伤（SCI）、创伤性脑损伤（TBI）和缺血性脑损伤（IBI））动物模型中最常见和最佳的神经保护雌激素。这些中枢神经系统损伤不仅是严重的健康问题，也给患者、家庭和社会带来了巨大的经济负担。来自这些CNS损伤的动物模型的研究提供了对E2的多种神经保护机制的见解，并且还表明在不久的将来将E2在治疗SCI、TBI和IBI中的治疗功效转化为人类的可能性。这些损伤的病理生理学包括肢体、手臂及其四肢的运动功能丧失、认知缺陷以及许多其他严重后果，包括危及生命的瘫痪、感染甚至死亡。E2治疗中枢神经系统损伤的潜在应用可能成为一种趋势，因为结果显示E2在SCI、TBI和IBI动物模型中具有显著的神经保护作用。本文描述了E2如何与雌激素受体的参与或不参与的合理机制，并提供了一个概述的E2在这三个中枢神经系统损伤在不同的动物模型中已知的神经保护作用。由于雌激素受体的激活在维持和影响正常生理学方面具有深远的意义，因此将E2治疗转化为临床用于人类CNS损伤的神经保护存在明显的障碍。虽然由于围绕E2的争议，E2可能还不是治疗CNS损伤的唯一分子，但其代谢物和衍生物或E2与另一种治疗剂的组合的神经保护作用在动物模型中显示出显著的影响，这可能会潜在地塑造人类这些CNS损伤的新治疗策略。
Among the estrogens that are biosynthesized in the human body, 17β-estradiol (estradiol or E2) is the most common and the best estrogen for neuroprotection in animal models of the central nervous system (CNS) injuries such as spinal cord injury (SCI), traumatic brain injury (TBI), and ischemic brain injury (IBI). These CNS injuries are not only serious health problems, but also enormous economic burden on the patients, their families, and the society at large. Studies from animal models of these CNS injuries provide insights into the multiple neuroprotective mechanisms of E2 and also suggest the possibility of translating the therapeutic efficacy of E2 in the treatment SCI, TBI, and IBI in humans in the near future. The pathophysiology of these injuries includes loss of motor function in the limbs, arms and their extremities, cognitive deficit, and many other serious consequences including life-threatening paralysis, infection, and even death. The potential application of E2 therapy to treat the CNS injuries may become a trend as the results are showing significant therapeutic benefits of E2 for neuroprotection when administered into the animal models of SCI, TBI, and IBI. This article describes the plausible mechanisms how E2 works with or without the involvement of estrogen receptors and provides an overview of the known neuroprotective effects of E2 in these three CNS injuries in different animal models. Because activation of estrogen receptors has profound implications in maintaining and also affecting normal physiology, there are notable impediments in translating E2 therapy to the clinics for neuroprotection in CNS injuries in humans. While E2 may not yet be the sole molecule for the treatment of CNS injuries due to the controversies surrounding it, the neuroprotective effects of its metabolite and derivative or combination of E2 with another therapeutic agent are showing significant impacts in animal models that can potentially shape the new treatment strategies for these CNS injuries in humans.