Omega-3 fatty acids and neurological injury
Omega-3 fatty acids and neurological injury
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DOI：
10.1016/j.plefa.2007.10.021
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发表时间：
2007-11-01
影响因子：
3
通讯作者：
Michael-Titus, Adina T.
中科院分区：
文献类型：
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作者：
Michael-Titus, Adina T.
对omega-3多不饱和脂肪酸（PUFA）的研究表明，这些化合物在神经病学和精神病学的几种适应症中具有治疗潜力。急性脊髓损伤（SCI）是一种具有毁灭性后果的疾病，目前尚无令人满意的治疗方法。与脊髓损伤相关的发病机制包括兴奋性毒性、氧化增加和炎症。我们在此回顾我们最近的研究，这些研究表明omega-3 PUFA在脊髓创伤中具有显著的神经保护潜力。在第一项研究中，我们在成年大鼠脊髓半切损伤后30分钟静脉注射a-亚麻酸（LNA）或二十二碳六烯酸（DHA）。omega-3 PUFA增加了神经元和神经胶质的存活率，并显著改善了神经系统的预后。在随后的研究中，我们在更严重的脊髓损伤压缩模型中测试了DHA。我们还探索了一种使用DHA的急慢性联合治疗方案。脊髓受压30分钟后静脉给予生理盐水或DHA。受伤后，生理盐水组接受标准对照饮食，而注射dha的动物在受伤后6周内接受对照或富含dha的饮食。我们评估了运动恢复，分析了细胞存活和轴突损伤的标志物，我们还研究了治疗对脊髓损伤后炎症反应和氧化应激的影响。我们发现，急性DHA治疗在受压性脊髓损伤后具有神经保护作用，即使治疗延迟至损伤后1小时。DHA注射增加了神经元和神经胶质细胞的存活率，DHA注射的效果通过在饮食中添加DHA而被放大。大鼠接受DHA注射和富含DHA的饮食治疗，在6周的神经系统预后方面表现明显更好。DHA给药后的组织分析显示，脂肪酸显著降低脂质过氧化、蛋白质氧化和RNA/DNA氧化，并诱导COX-2。在小鼠面神经损伤模型中进行的平行研究也显示，神经损伤后，长期饮食给药DHA具有促进再生的作用。这些观察结果表明，用omega-3 PUFA治疗可能是一种很有前途的治疗神经损伤的方法。(C) 2007 Elsevier Ltd.版权所有。
Studies with omega-3 polyunsaturated fatty acids (PUFA) have shown that these compounds have therapeutic potential in several indications in neurology and psychiatry. Acute spinal cord injury (SCI) is an event with devastating consequences, and no satisfactory treatment is available at present. The pathogenetic mechanisms associated with SCI include excitotoxicity, increased oxidation and inflammation. We review here our recent studies, which suggest that omega-3 PUFA have significant neuroprotective potential in spinal cord trauma. In a first study, we administered an intravenous bolus of a-linolenic acid (LNA) or docosahexaenoic acid (DHA) 30 min after spinal cord hemisection injury in adult rats. The omega-3 PUFA led to increased neuronal and glial survival, and a significantly improved neurological outcome. In subsequent studies, we tested DHA in a more severe compression model of SCI. We also explored a combined acute and chronic treatment regime using DHA. Saline or DHA was administered intravenously 30 min after compression of the spinal cord. After injury, the saline group received a standard control diet, whereas DHA-injected animals received either a control or a DHA-enriched diet for 6 weeks following injury. We assessed locomotor recovery and analysed markers for cell survival and axonal damage, and we also investigated the effects of the treatment on the inflammatory reaction and the oxidative stress that follow SCI. We showed that the acute DHA treatment is neuroprotective after compression SCI, even if the treatment is delayed up to an hour after injury. The DHA injection led to an increased neuronal and glial cell survival, and the effect of the DHA injection was amplified by addition of DHA to the diet. Rats treated with a DHA injection and a DHA-enriched diet performed significantly better at 6 weeks in terms of neurological outcome. The analysis of the tissue after DHA administration showed that the fatty acid significantly reduced lipid peroxidation, protein oxidation and RNA/DNA oxidation, and the induction of COX-2. Parallel studies in a facial nerve injury model in mice also showed pro-regenerative effects of chronic dietary administration of DHA after nerve lesion. These observations suggest that treatment with omega-3 PUFA could represent a promising therapeutic approach in the management of neurological injury. (C) 2007 Elsevier Ltd. All rights reserved.