ApoE mimetic ameliorates motor deficit and tissue damage in rat spinal cord injury
ApoE mimetic ameliorates motor deficit and tissue damage in rat spinal cord injury
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DOI：
10.1002/jnr.23371
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发表时间：
2014-07-01
影响因子：
4.2
通讯作者：
Sheng, Huaxin
中科院分区：
文献类型：
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作者：
Wang, Ruihua;Hong, Jun;Sheng, Huaxin
载脂蛋白E（apoE）是一种负责转运脂质和胆固醇的血浆蛋白，调节中枢神经系统对损伤的反应。来源于apoE受体结合区的小肽可以模拟apoE全蛋白的一些重要生物活性，对脑损伤具有神经保护作用。我们测试了COG 1410，一种apoE模拟肽，是否在大鼠脊髓损伤（SCI）模型中提供保护。在T8处通过皮质撞击器械造成创伤性损伤。将损伤大鼠随机分为四个治疗组：溶媒组、0.15、0.3或0.6 mg/kg COG 1410组;假手术大鼠接受溶媒组。分别于伤前、伤后1、3、7、14天进行Basso、Beattie、Bresnahan神经功能评分。在第14天评价组织学变化。所有受伤的大鼠在受伤后的第一周内体重减轻。在用COG 1410处理的大鼠中，体重恢复显著改善。机械撞击导致严重的运动缺陷，大多数动物在伤后24小时的BBB评分为0-1。COG 1410治疗的大鼠在损伤后14天表现出显著改善的功能恢复和改善的运动缺陷。组织学分析显示，COG 1410组在损伤部位具有显著减小的损伤尺寸，较大的保留的luxol坚牢蓝染色区域，以及损伤周围区域中更多可见的神经元。小胶质细胞活化也被显著抑制。这些发现表明，这种apoE模拟物有效地改善了大鼠SCI后的神经和组织学结果，并且该效果与抑制小胶质细胞活化有关。(c)2014年威利期刊公司
Apolipoprotein E (apoE), a plasma protein responsible for transporting lipid and cholesterol, modulates responses of the central nervous system to injury. Small peptides derived from the receptor-binding region of apoE can simulate some important bioactivities of apoE holoprotein and offer neuroprotection against brain injury. We tested whether COG1410, an apoE-mimetic peptide, provides protection in a rat model of spinal cord injury (SCI). Traumatic injury was created at T8 by a cortical impact device. Injured rats were randomized to four treatment groups: vehicle, 0.15, 0.3, or 0.6 mg/kg COG1410; sham surgery rats received vehicle. Basso, Beattie, Bresnahan neurological score was evaluated prior to injury and at 1, 3, 7, and 14 days after injury. Histological changes were evaluated at 14 days. All injured rats lost body weight during the first week following injury. Body weight recovery was significantly improved in rats treated with COG1410. Mechanical impact resulted in severe motor deficit, and most animals had a BBB score of 0-1 at 24 hours postinjury. COG1410-treated rats showed significantly improved functional recovery and ameliorated motor deficit at 14 days postinjury. Histological analysis showed that COG1410 groups had a significantly reduced lesion size at the site of injury, a larger preserved luxol fast blue-stained area, and more visible neurons in the surrounding area of injury. Microglial activation was also significantly suppressed. These findings indicate that this apoE mimetic effectively improved neurological and histological outcome following SCI in rats, and the effect was associated with inhibition of microglial activation. (c) 2014 Wiley Periodicals, Inc.