Chaovipoch Pimonporn, Jelks Karen A Bozak, Gerhold Lynnette M, West Eric J, Chongthammakun Sukumal, Floyd Candace L
Department of Neurological Surgery, University of California, Davis, California 95616, USA.
J Neurotrauma. 2006 Jun;23(6):830-52. doi: 10.1089/neu.2006.23.830.
The neuroprotective effects of 17 beta -estradiol have been shown in models of central nervous system injury, including ischemia, brain injury, and more recently, spinal cord injury (SCI). Recent epidemiological trends suggest that SCIs in elderly women are increasing; however, the effects of menopause on estrogen-mediated neuroprotection are poorly understood. The objective of this study was to evaluate the effects of 17beta-estradiol and reproductive aging on motor function, neuronal death, and white matter sparing after SCI of post- and pre-menopausal rats. Two-month-old or 1- year-old female rats were ovariectomized and implanted with a silastic capsule containing 180 microg/mL of 17beta-estradiol or vehicle. Complete crush SCI at T8-9 was performed 1 week later. Additional animals of each age group were left ovary-intact but were spinal cord injured. The Basso, Beattie, Bresnahan (BBB) locomotor test was performed. Spinal cords were collected on post-SCI days 1, 7, and 21, and processed for histological markers. Administration of 17beta-estradiol to ovariectomized rats improved recovery of hind-limb locomotion, increased white matter sparing, and decreased apoptosis in both the post- and pre-menopausal rats. Also, ovary-intact 1-year-old rats did worse than ovary-intact 2-month-old rats, suggesting that endogenous estrogen confers neuroprotection in young rats, which is lost in older animals. Taken together, these data suggest that estrogen is neuroprotective in SCI and that the loss of endogenous estrogen-mediated neuroprotective seen in older rats can be attenuated with exogenous administration of 17beta-estradiol.
17β-雌二醇的神经保护作用已在中枢神经系统损伤模型中得到证实，包括缺血性损伤、脑损伤，以及最近发现的脊髓损伤（SCI）。近期的流行病学趋势表明，老年女性脊髓损伤的发生率正在上升；然而，绝经对雌激素介导的神经保护作用的影响却知之甚少。本研究的目的是评估17β-雌二醇和生殖衰老对绝经后和绝经前大鼠脊髓损伤后运动功能、神经元死亡和白质保留的影响。将2月龄或1岁龄的雌性大鼠进行卵巢切除术，并植入含有180μg/mL 17β-雌二醇或赋形剂的硅橡胶胶囊。1周后，在T8-9水平进行完全性脊髓挤压损伤。每个年龄组的其他动物保留卵巢，但进行脊髓损伤。进行Basso、Beattie、Bresnahan（BBB）运动测试。在脊髓损伤后的第1、7和21天收集脊髓，并进行组织学标记物检测。对去卵巢大鼠给予17β-雌二醇可改善后肢运动功能的恢复，增加白质保留，并减少绝经后和绝经前大鼠的细胞凋亡。此外，保留卵巢的1岁龄大鼠比保留卵巢的2月龄大鼠恢复得更差，这表明内源性雌激素在年轻大鼠中具有神经保护作用，而在老年动物中则丧失。综上所述，这些数据表明雌激素在脊髓损伤中具有神经保护作用，并且老年大鼠中内源性雌激素介导的神经保护作用的丧失可通过外源性给予17β-雌二醇来减轻。
