Delayed Docosahexaenoic Acid Treatment Combined with Dietary Supplementation of Omega-3 Fatty Acids Promotes Long-Term Neurovascular Restoration After Ischemic Stroke.
Delayed Docosahexaenoic Acid Treatment Combined with Dietary Supplementation of Omega-3 Fatty Acids Promotes Long-Term Neurovascular Restoration After Ischemic Stroke.
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延迟二十二碳六烯酸治疗结合膳食补充 Omega-3 脂肪酸可促进缺血性中风后长期神经血管恢复
DOI：
10.1007/s12975-016-0498-y
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发表时间：
2016-12
影响因子：
6.9
通讯作者：
Shi, Yejie
中科院分区：
文献类型：
--
作者：
Pu, Hongjian;Jiang, Xiaoyan;Hu, Xiaoming;Xia, Jinchao;Hong, Dandan;Zhang, Wenting;Gao, Yanqin;Chen, Jun;Shi, Yejie
预防性膳食摄入ω-3多不饱和脂肪酸（n-3 PUFA）已被证明可显著改善缺血性脑损伤。然而，n-3多不饱和脂肪酸管理中风后的治疗效果，特别是其对神经血管重塑和长期神经功能恢复的影响，迄今尚未得到充分的表征。在这项研究中，我们调查了n-3 PUFA补充剂以及与二十二碳六烯酸（DHA）注射剂联合使用对长期中风结局的影响。使小鼠经受短暂大脑中动脉闭塞（MCAO），然后随机分配至4组以接受：1）低剂量的n-3 PUFA作为媒介物对照; 2）腹膜内DHA注射; 3）n-3 PUFA膳食补充剂;或4）2）和3）的组合治疗。神经功能缺损和脑萎缩，神经发生，血管生成和胶质瘢痕形成进行了评估，直到28天后MCAO。结果显示，第2组和第3组仅显示出卒中后组织损失的边际减少和认知缺陷的衰减。有趣的是，与仅单次治疗的组2和组3相比，组4表现出显著减少的组织萎缩和改善的认知功能。从机制上讲，联合治疗促进了卒中后神经发生和血管生成，并减少了胶质瘢痕形成，所有这些都与Morris水迷宫中空间记忆的改善显著相关。这些结果证明了一种有效的治疗方案，以增强MCAO小鼠模型中的神经血管恢复和长期认知恢复。因此，脑卒中后DHA治疗和n-3 PUFA膳食补充剂的组合可能是脑卒中或相关脑部疾病的潜在临床可转化疗法。
Prophylactic dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs) has been shown to remarkably ameliorate ischemic brain injury. However, the therapeutic efficacy of n-3 PUFA administration post stroke, especially its impact on neurovascular remodeling and long-term neurological recovery, has not been fully characterized thus far. In this study, we investigated the effect of n-3 PUFA supplementation, as well as in combination with docosahexaenoic acid (DHA) injections, on long-term stroke outcomes. Mice were subjected to transient middle cerebral artery occlusion (MCAO) before randomly assigned to 4 groups to receive: 1) low dose of n-3 PUFAs as the vehicle control; 2) intraperitoneal DHA injections; 3) n-3 PUFA dietary supplement; or 4) combined treatment of 2) and 3). Neurological deficits and brain atrophy, neurogenesis, angiogenesis, and glial scar formation were assessed up to 28 days after MCAO. Results revealed that groups 2 and 3 showed only marginal reduction in post-stroke tissue loss and attenuation of cognitive deficits. Interestingly, group 4 exhibited significantly reduced tissue atrophy and improved cognitive functions compared to groups 2 and 3 with just a single treatment. Mechanistically, the combined treatment promoted post-stroke neurogenesis and angiogenesis, and reduced glial scar formation, all of which significantly correlated with the improved spatial memory in the Morris water maze. These results demonstrate an effective therapeutic regimen to enhance neurovascular restoration and long-term cognitive recovery in the mouse model of MCAO. Combined post-stroke DHA treatment and n-3 PUFA dietary supplementation thus may be a potential clinically-translatable therapy for stroke or related brain disorders.
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影响因子：
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