Mahmood Asim, Goussev Anton, Kazmi Humaira, Qu Changsheng, Lu Dunyue, Chopp Michael
Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan, USA.
Neurosurgery. 2009 Jul;65(1):187-91; discussion 191-2. doi: 10.1227/01.NEU.0000343540.24780.D6.
This study was designed to investigate the long-term effects of simvastatin treatment after traumatic brain injury (TBI) in rats.
Adult female Wistar rats (n = 24) were injured with controlled cortical impact and divided into 3 groups. The first 2 groups were treated with simvastatin (0.5 or 1.0 mg/kg) administered orally for 14 days starting 1 day after TBI. The third group (control) received phosphate-buffered saline orally for 14 days. Neurological functional outcome was measured with modified neurological severity scores performed 1 day before TBI; on days 1, 4, 7, 14 after TBI; and biweekly thereafter. All animals were sacrificed 3 months after TBI. Brain tissues of half of the animals were processed for preparation of paraffin-embedded sections for immunohistological studies. The remaining half were frozen for enzyme-linked immunosorbent assay studies for quantification of brain-derived neurotrophic factor (BDNF) in the hippocampus and cortex.
The results showed that both doses of simvastatin significantly improved functional outcome compared with the control, with no difference between the 2 doses. Simvastatin treatment of 1.0 mg/kg increased the number of morphologically intact neurons in the hippocampus, but treatment of 0.5 mg/kg had no significant effect. Enzyme-linked immunosorbent assay studies showed that 0.5 mg/kg simvastatin significantly increased BDNF levels within the hippocampus, but 1.0 mg/kg had no significant effect. Neither dose had any effect on BDNF levels within the cortex.
Simvastatin treatment provides long-lasting functional improvement after TBI in rats. It also enhances neuronal survival in the hippocampus and increases BDNF levels in the hippocampus secondary to simvastatin treatment.
本研究旨在探讨辛伐他汀治疗对大鼠创伤性脑损伤（TBI）后的长期影响。
成年雌性Wistar大鼠（n = 24）接受控制性皮质撞击损伤，并分为3组。前两组在TBI后1天开始口服给予辛伐他汀（0.5或1.0 mg/kg），持续14天。第三组（对照组）口服磷酸盐缓冲盐水14天。在TBI前1天、TBI后第1、4、7、14天以及此后每两周进行改良神经功能严重程度评分，以测量神经功能结局。所有动物在TBI后3个月处死。一半动物的脑组织用于制备石蜡包埋切片，进行免疫组织学研究。其余一半冷冻用于酶联免疫吸附测定研究，以定量海马体和皮质中的脑源性神经营养因子（BDNF）。
结果显示，与对照组相比，两种剂量的辛伐他汀均显著改善了功能结局，且两种剂量之间无差异。1.0 mg/kg的辛伐他汀治疗增加了海马体中形态完整神经元的数量，但0.5 mg/kg的治疗无显著效果。酶联免疫吸附测定研究表明，0.5 mg/kg的辛伐他汀显著提高了海马体内的BDNF水平，但1.0 mg/kg无显著效果。两种剂量对皮质内的BDNF水平均无影响。
辛伐他汀治疗可使大鼠TBI后功能得到长期改善。它还可增强海马体中的神经元存活，并因辛伐他汀治疗而增加海马体中的BDNF水平。
