Instituto Cajal, CSIC, Madrid, Spain.
J Neuroendocrinol. 2012 Jan;24(1):183-90. doi: 10.1111/j.1365-2826.2011.02156.x.
Neuroinflammation comprises a feature of many neurological disorders that is accompanied by the activation of glial cells and the release of pro-inflammatory cytokines and chemokines. Such activation is a normal response oriented to protect neural tissue and it is mainly regulated by microglia and astroglia. However, excessive and chronic activation of glia may lead to neurotoxicity and may be harmful for neural tissue. The ovarian hormone oestradiol exerts protective actions in the central nervous system that, at least in part, are mediated by a reduction of reactive gliosis. Several selective oestrogen receptor modulators may also exert neuroprotective effects by controlling glial inflammatory responses. Thus, tamoxifen and raloxifene decrease the inflammatory response caused by lipopolysaccharide, a bacterial endotoxin, in mouse and rat microglia cells in vitro. Tamoxifen and raloxifene are also able to reduce microglia activation in the brain of male and female rats in vivo after the peripheral administration of lipopolysaccharide. In addition, tamoxifen decreases the microglia inflammatory response induced by irradiation. Furthermore, treatment with tamoxifen and raloxifene resulted in a significant reduction of the number of reactive astrocytes in the hippocampus of young, middle-aged and older female rats after a stab wound injury. Tamoxifen, raloxifene and the new selective oestrogen receptor modulators ospemifene and bazedoxifene decrease the expression and release of interleukine-6 and interferon-γ inducible protein-10 in cultured astrocytes exposed to lipopolysaccharide. Ospemifene and bazedoxifene exert anti-inflammatory effects in astrocytes by a mechanism involving classical oestrogen receptors and the inhibition of nuclear factor-kappa B p65 transactivation. These data suggest that oestrogenic compounds are candidates to counteract brain inflammation under neurodegenerative conditions by targeting the production and release of pro-inflammatory molecules by glial cells.
神经炎症是许多神经紊乱的特征之一，伴随着神经胶质细胞的激活以及促炎细胞因子和趋化因子的释放。这种激活是一种以保护神经组织为导向的正常反应，主要由小胶质细胞和星形胶质细胞调节。然而，胶质细胞的过度和慢性激活可能导致神经毒性，可能对神经组织有害。卵巢激素雌激素在中枢神经系统中发挥保护作用，至少部分是通过减少反应性神经胶质增生来介导的。几种选择性雌激素受体调节剂也可以通过控制神经胶质炎症反应发挥神经保护作用。因此，他莫昔芬和雷洛昔芬可减少脂多糖（一种细菌内毒素）在体外诱导的小鼠和大鼠小胶质细胞的炎症反应。他莫昔芬和雷洛昔芬也能够减少脂多糖外周给药后雄性和雌性大鼠大脑中的小胶质细胞激活。此外，他莫昔芬可减少辐射诱导的小胶质细胞炎症反应。此外，他莫昔芬和雷洛昔芬治疗可显著减少年轻、中年和老年雌性大鼠海马中反应性星形胶质细胞的数量，这些大鼠在刺伤损伤后。他莫昔芬、雷洛昔芬和新的选择性雌激素受体调节剂奥昔孕胺和巴多昔芬可减少脂多糖暴露的星形胶质细胞中白细胞介素-6 和干扰素-γ诱导蛋白-10 的表达和释放。奥昔孕胺和巴多昔芬通过涉及经典雌激素受体和核因子-κB p65 反式激活抑制的机制在星形胶质细胞中发挥抗炎作用。这些数据表明，雌激素化合物是通过靶向神经胶质细胞产生和释放促炎分子来对抗神经退行性条件下脑炎症的候选药物。
