Xie Qing, Guan Jian, Wu Gang, Xi Guohua, Keep Richard F, Hua Ya
Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Acta Neurochir Suppl. 2011;111:271-5. doi: 10.1007/978-3-7091-0693-8_45.
Tamoxifen is a selective estrogen receptor modulator. In this study we investigated whether or not tamoxifen reduces intracerebral hemorrhage (ICH)-induced brain injury in rats. In all experiments, adult male Sprague-Dawley rats received an injection of 100 μL autologous whole blood into the right basal ganglia. In the first set of experiments, rats were treated with tamoxifen (2.5 mg/kg or 5 mg/kg, i.p.) or vehicle 2 and 24 h after ICH and were killed at day 3 for brain edema measurement. In the second set of experiments, rats were treated with tamoxifen (5 mg/kg) or vehicle and magnetic resonance imaging (MRI), and behavior tests were performed at days 1, 7, 14 and 28. Rats were killed at day 28 for brain histology. We found that tamoxifen at 5 but not at 2.5 mg/kg reduced perihematomal brain edema at day 3 (p<0.05). Brain histology showed that tamoxifen reduced caudate atrophy at day 28 (p<0.01). Tamoxifen also improved functional outcome (p<0.05). MRI demonstrated a tendency to smaller T2* lesions in tamoxifen-treated rats. However, two out of five rats treated with tamoxifen developed hydrocephalus. These results suggest that tamoxifen has neuroprotective effects in ICH, but the cause of hydrocephalus development following tamoxifen treatment needs to be examined further.
他莫昔芬是一种选择性雌激素受体调节剂。在本研究中，我们调查了他莫昔芬是否能减轻大鼠脑出血（ICH）所致的脑损伤。在所有实验中，成年雄性Sprague-Dawley大鼠右侧基底节注射100 μL自体全血。在第一组实验中，大鼠在脑出血后2小时和24小时接受他莫昔芬（2.5 mg/kg或5 mg/kg，腹腔注射）或赋形剂治疗，并在第3天处死以测量脑水肿。在第二组实验中，大鼠接受他莫昔芬（5 mg/kg）或赋形剂治疗并进行磁共振成像（MRI），并在第1、7、14和28天进行行为测试。大鼠在第28天处死以进行脑组织学检查。我们发现，5 mg/kg而非2.5 mg/kg的他莫昔芬可减轻第3天的血肿周围脑水肿（p<0.05）。脑组织学检查显示，他莫昔芬可减轻第28天的尾状核萎缩（p<0.01）。他莫昔芬还改善了功能结局（p<0.05）。MRI显示他莫昔芬治疗的大鼠T2*病变有变小的趋势。然而，接受他莫昔芬治疗的5只大鼠中有2只发生了脑积水。这些结果表明，他莫昔芬在脑出血中具有神经保护作用，但他莫昔芬治疗后发生脑积水的原因需要进一步研究。
