Estrogens attenuate neuronal injury due to hemoglobin, chemical hypoxia, and excitatory amino acids in murine cortical cultures

被引:123
作者
Regan, RF
Guo, YP
机构
[1] Division of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19107
关键词
brain injury; brain ischemia; cortical neuron; equilin; estradiol; free radical; glutamate; lipid peroxidation;
D O I
10.1016/S0006-8993(97)00437-X
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
A growing body of evidence supports the hypothesis that estrogens may be beneficial in Alzheimer's disease and other neurodegenerative processes. Less is known of their therapeutic potential in acute CNS insults. In this study, we assessed the effect of estrogens in three injury paradigms that may be relevant to CNS hemorrhage, trauma, and ischemia. Supraphysiologic concentrations of 17 beta-estradiol, estrone, or equilin attenuated neuronal loss due to prolonged exposure to the pro-oxidant hemoglobin, with complete protection at 10 mu M. Most of this effect persisted despite concomitant treatment with the antiestrogen ICI 182,780 or the protein synthesis inhibitor cycloheximide. In contrast, the non-estrogenic steroid methylprednisolone, which is currently in clinical use in spinal cord injury, reduced neuronal loss by only about 30%. High concentrations of equilin or estrone also attenuated the submaximal neuronal injury induced by 3.5-4.5 h exposure to the cytochrome oxidase inhibitor sodium azide, with near complete protection at 30 mu M. Estrogens had a weaker and somewhat variable effect on pure excitotoxic injury, reducing neuronal loss due to 24 h kainate exposure by about half, and due to 24 h NMDA exposure by 15-65%; similar neuroprotection was provided by the antioxidant 21-aminosteroid U74500A. These results suggest that estrogens may be beneficial in acute CNS injuries associated with oxidative and excitotoxic stress. Investigation of high dose estro en therapy in in vivo models of CNS hemorrhage, trauma, and ischemia is warranted. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:133 / 140
页数:8
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