Raghava Narayan, Das Bhaskar C, Ray Swapan K
Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Neurosci Neuroecon. 2017;6:15-29. doi: 10.2147/NAN.S105134. Epub 2017 Jul 4.
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.
在人体生物合成的雌激素中，17β-雌二醇（雌二醇或E2）最为常见，并且在中枢神经系统（CNS）损伤（如脊髓损伤（SCI）、创伤性脑损伤（TBI）和缺血性脑损伤（IBI））的动物模型中是最具神经保护作用的雌激素。这些CNS损伤不仅是严重的健康问题，也给患者、其家庭以及整个社会带来了巨大的经济负担。对这些CNS损伤动物模型的研究揭示了E2的多种神经保护机制，也提示了在不久的将来将E2的治疗效果转化用于人类SCI、TBI和IBI治疗的可能性。这些损伤的病理生理学包括四肢、手臂及其末端的运动功能丧失、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。随着研究结果显示E2在SCI、TBI和IBI动物模型中给药时具有显著的神经保护治疗益处，E2疗法在治疗CNS损伤方面的潜在应用可能会成为一种趋势。本文描述了E2在有无雌激素受体参与的情况下发挥作用的可能机制，并概述了E2在不同动物模型中对这三种CNS损伤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方面具有深远意义，将E2疗法转化用于人类CNS损伤神经保护的临床应用存在显著障碍。虽然由于围绕E2的争议，它可能尚未成为治疗CNS损伤的唯一分子，但其代谢产物和衍生物的神经保护作用，或E2与另一种治疗药物的联合应用，在动物模型中显示出显著影响，这可能会为人类这些CNS损伤塑造新的治疗策略。
