Horsburgh Karen, Macrae I Mhairi, Carswell Hilary
Wellcome Surgical Institute and Hugh Fraser Neuroscience Laboratories, Glasgow, Scotland, UK.
J Cereb Blood Flow Metab. 2002 Oct;22(10):1189-95. doi: 10.1097/01.wcb.0000037991.07114.4e.
Estrogen can ameliorate brain damage in experimental models of focal cerebral ischemia., estrogen increases levels of apolipoprotein E (apoE), which also has neuroprotective effects in brain injury. The authors tested the hypotheses that physiologically relevant levels of 17beta-estradiol are neuroprotective in global cerebral ischemia and that neuroprotection is mediated via apoE. In the first study, subcutaneous implants of 17beta-estradiol were tested in female C57Bl/6J mice (ovariectomized and nonovariectomized) and plasma levels measured by radioimmunoassay to validate that physiologically relevant levels could be achieved. In the second study, female C57Bl/6J and apoE-deficient mice were ovariectomized and implanted with 17beta-estradiol or placebo pellet. Two weeks later, transient global ischemia was induced by bilateral carotid artery occlusion and the mice killed after 72 hours. Ischemic and normal neurons were counted in the caudate nucleus and CA1 pyramidal cell layer and the percentage of neuronal damage was compared between the treated groups. In C57Bl/6J mice, there was less neuronal damage in the 17beta-estradiol-treated group compared with placebo group in the caudate nucleus (15 +/- 20% versus 39 +/- 27%, = 0.02) and in the CA1 pyramidal cell layer (1.8 +/- 2% versus 10 +/- 14%, = 0.08). In contrast, neuronal damage was not significantly different between the 17beta-estradiol and placebo groups in apoE-deficient mice in the caudate nucleus (47 +/- 35% versus 53 +/- 29%, = 0.7) or in the CA1 pyramidal cell layer (24 +/- 19% versus 24 +/- 19%, = 1.0). The data indicate a neuroprotective role for estrogen in global ischemia, the mechanism of which is apoE-dependent.
雌激素可改善局灶性脑缺血实验模型中的脑损伤。雌激素可提高载脂蛋白E（apoE）水平，而载脂蛋白E在脑损伤中也具有神经保护作用。作者检验了以下假设：生理相关水平的17β-雌二醇在全脑缺血中具有神经保护作用，且神经保护作用是通过载脂蛋白E介导的。在第一项研究中，对雌性C57Bl/6J小鼠（去卵巢和未去卵巢）进行皮下植入17β-雌二醇，并通过放射免疫测定法测量血浆水平，以验证能否达到生理相关水平。在第二项研究中，对雌性C57Bl/6J和载脂蛋白E缺陷小鼠进行去卵巢，并植入17β-雌二醇或安慰剂丸剂。两周后，通过双侧颈动脉闭塞诱导短暂性全脑缺血，并在72小时后处死小鼠。对尾状核和CA1锥体细胞层中的缺血和正常神经元进行计数，并比较各治疗组之间的神经元损伤百分比。在C57Bl/6J小鼠中，与安慰剂组相比，17β-雌二醇治疗组在尾状核中的神经元损伤较少（15±20%对39±27%，P=0.02），在CA1锥体细胞层中也较少（1.8±2%对10±14%，P=0.08）。相比之下，在载脂蛋白E缺陷小鼠中，17β-雌二醇组和安慰剂组在尾状核中的神经元损伤无显著差异（47±35%对53±29%，P=0.7），在CA1锥体细胞层中也无显著差异（24±19%对24±19%，P=1.0）。数据表明雌激素在全脑缺血中具有神经保护作用，其机制依赖于载脂蛋白E。
