A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury
A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury
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DOI：
10.1093/brain/awm223
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发表时间：
2007-11-01
期刊：
影响因子：
14.5
通讯作者：
Michael-Titus, A. T.
中科院分区：
文献类型：
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作者：
Huang, W. L.;King, V. R.;Michael-Titus, A. T.
先前的研究表明，ω-3多不饱和脂肪酸如α-亚麻酸和二十二碳六烯酸（DHA）在啮齿动物脊髓损伤（SCI）模型中具有神经保护作用。然而，这些影响的作用机制尚未阐明，最佳治疗方案仍有待确定。因此，我们进行了一个详细的分析DHA的影响，在成年大鼠胸部压缩脊髓损伤。将盐水或DHA（250 nmol/kg）静脉内（i. v.）压缩后30分钟。损伤后，生理盐水组接受标准对照饮食1或6周，而DHA注射组动物接受对照或富含DHA的饮食（400 mg/kg/天）1或6周。其他组在损伤后仅接受富含DHA的饮食1周，或接受急性DHA（250 nmol/kg; i. v.）治疗延迟至损伤后3小时。我们还评估了损伤部位的氧化应激和炎症反应，神经元和少突胶质细胞的存活和轴突损伤以及运动恢复。在24小时，脂质过氧化，蛋白质氧化，RNA/DNA氧化和环氧合酶-2的诱导都显着减少静脉注射DHA管理。在第1周和第6周，巨噬细胞募集减少，神经元和少突胶质细胞存活率大幅增加。6周时轴突损伤减轻。运动恢复从第4天开始改善，并持续长达6周。除了急性DHA注射之外，用富含DHA的饮食治疗的大鼠在1周时与急性DHA治疗的动物没有显著差异，但在6周时显示出功能和组织学结果的额外改善。如果急性注射延迟至损伤后3小时，或者如果仅通过饮食给予DHA 1周，则DHA治疗无效。我们在临床相关的SCI模型中的研究结果表明，通过将初始急性静脉注射DHA与持续的膳食补充剂相结合，可以获得显著的神经保护作用。鉴于富含omega- 3脂肪酸的制剂的安全性和耐受性已经得到充分证明，这种组合DHA治疗方案值得考虑作为一种非常有前途的SCI管理方法。
Previous studies have shown that omega-3 polyunsaturated fatty acids such as alpha-linolenic acid and docosahexaenoic acid (DHA) are neuroprotective in models of spinal cord injury (SCI) in rodents. However, the mechanism of action underlying these effects has not been elucidated, and the optimum treatment regime remains to be defined. We have therefore carried out a detailed analysis of the effects of DHA in adult rats subject to thoracic compression SCI. Saline or DHA (250 nmol/kg) was administered intravenously (i.v.) 30 min after compression. After injury, the saline group received a standard control diet for 1 or 6 weeks, whereas DHA-injected animals received either a control or a DHA-enriched diet (400mg/kg/day) for 1 or 6 weeks. Other groups received a DHA-enriched diet only for 1 week following injury, or received acute DHA (250 nmol/kg; i.v.) treatment delayed up to 3 h after injury. We also assessed oxidative stress and the inflammatory reaction at the injury site, neuronal and oligodendrocyte survival and axonal damage and the locomotor recovery. At 24 h, lipid peroxidation, protein oxidation, RNA/DNA oxidation and the induction of cyclooxygenase-2 were all significantly reduced by i.v. DHA administration. At 1 week and 6 weeks, macrophage recruitment was reduced and neuronal and oligodendrocyte survival was substantially increased. Axonal injury was reduced at 6 weeks. Locomotor recovery was improved from day 4, and sustained up to 6 weeks. Rats treated with a DHA-enriched diet in addition to the acute DHA injection were not significantly different from the acute DHA-treated animals at 1 week, but at 6 weeks showed additional improvements in both functional and histological outcomes. DHA treatment was ineffective if the acute injection was delayed until 3 h post-injury, or if the DHA was administered for 1 week solely by diet. Our results in a clinically relevant model of SCI show that significant neuroprotection can be obtained by combining an initial acute i.v. injection of DHA with a sustained dietary supplementation. Given that the safety and tolerability of preparations enriched in omega- 3 fatty acids is already well-documented, such a combined DHA treatment regime deserves consideration as a very promising approach to SCI management.