A Post-stroke Therapeutic Regimen with Omega-3 Polyunsaturated Fatty Acids that Promotes White Matter Integrity and Beneficial Microglial Responses after Cerebral Ischemia.
A Post-stroke Therapeutic Regimen with Omega-3 Polyunsaturated Fatty Acids that Promotes White Matter Integrity and Beneficial Microglial Responses after Cerebral Ischemia.
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含有 Omega-3 多不饱和脂肪酸的中风后治疗方案可促进脑缺血后白质完整性和有益的小胶质细胞反应
DOI：
10.1007/s12975-016-0502-6
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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：
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作者：
Jiang, Xiaoyan;Pu, Hongjian;Hu, Xiaoming;Wei, Zhishuo;Hong, Dandan;Zhang, Wenting;Gao, Yanqin;Chen, Jun;Shi, Yejie
缺血性卒中引起的白色物质损伤可诱发感觉运动障碍，持续的促炎反应可使其进一步恶化。我们以前报道过，延迟和重复使用omega-3多不饱和脂肪酸（n-3 PUFA）治疗可改善缺血性卒中后的空间认知功能和海马完整性。在本研究中，我们报告了一种中风后n-3 PUFA治疗方案，不仅可以保护灰质中的神经元损失，还可以促进白色物质的完整性。从大脑中动脉闭塞（MCAO）60分钟后2小时开始，小鼠随机分配接受腹腔内注射二十二碳六烯酸（DHA）（10 mg/kg，每天一次，持续14天），单独或与膳食鱼油（FO）补充剂的组合，从MCAO后5天开始。在MCAO后28天检查感觉运动功能、灰质和白色物质损伤以及小胶质细胞反应。我们的研究结果表明，DHA和FO联合治疗促进长期感觉运动恢复，并表现出比单独注射DHA更大的有益效果。从机制上讲，n-3 PUFA不仅对白色物质组分（如少突胶质细胞）提供直接保护，而且还增强了小胶质细胞M2极化，这可能对白色物质修复很重要。值得注意的是，改善的白色物质完整性和增加的M2小胶质细胞与n-3 PUFA治疗后中风后感觉运动缺陷的减轻密切相关。总之，我们的研究结果表明，中风后DHA注射与FO膳食补充剂相结合，有利于白色物质的恢复和小胶质细胞的反应，从而决定了长期的功能改善。
White matter injury induced by ischemic stroke elicits sensorimotor impairments, which can be further deteriorated by persistent proinflammatory responses. We previously reported that delayed and repeated treatments with omega-3 polyunsaturated fatty acids (n-3 PUFAs) improve spatial cognitive functions and hippocampal integrity after ischemic stroke. In the present study, we report a post-stroke n-3 PUFA therapeutic regimen that not only confers protection against neuronal loss in the gray matter but also promotes white matter integrity. Beginning 2 h after 60 min of middle cerebral artery occlusion (MCAO), mice were randomly assigned to receive intraperitoneal docosahexaenoic acid (DHA) injections (10 mg/kg, daily for 14 days), alone or in combination with dietary fish oil (FO) supplements starting 5 days after MCAO. Sensorimotor functions, gray and white matter injury, and microglial responses were examined up to 28 days after MCAO. Our results showed that DHA and FO combined treatment-facilitated long-term sensorimotor recovery and demonstrated greater beneficial effect than DHA injections alone. Mechanistically, n-3 PUFAs not only offered direct protection on white matter components, such as oligodendrocytes, but also potentiated microglial M2 polarization, which may be important for white matter repair. Notably, the improved white matter integrity and increased M2 microglia were strongly linked to the mitigation of sensorimotor deficits after stroke upon n-3 PUFA treatments. Together, our results suggest that post-stroke DHA injections in combination with FO dietary supplement benefit white matter restoration and microglial responses, thereby dictating long-term functional improvements.
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影响因子：
6.9
作者：
Khan, Mohammad Badruzzaman;Hoda, Md Nasrul;Vaibhav, Kumar;Giri, Shailendra;Wang, Philip;Waller, Jennifer L.;Ergul, Adviye;Dhandapani, Krishnan M.;Fagan, Susan C.;Hess, David C.
通讯作者：
Hess, David C.
N-3 PUFA补充有益于对髓磷脂病理的小胶质反应。
影响因子：
4.6
作者：
Chen S;Zhang H;Pu H;Wang G;Li W;Leak RK;Chen J;Liou AK;Hu X
通讯作者：
Hu X
中枢神经系统损伤中小胶质细胞作用的神经生物学：受体介导的信号传导机制和功能作用
影响因子：
6.7
作者：
Hu, Xiaoming;Liou, Anthony K. F.;Leak, Rehana K.;Xu, Mingyue;An, Chengrui;Suenaga, Jun;Shi, Yejie;Gao, Yanqin;Zheng, Ping;Chen, Jun
通讯作者：
Chen, Jun
Docosahexaenoic酸改善了行为，并减轻大鼠局灶性脑缺血引起的血脑屏障损伤。
DOI：
10.1186/s13231-014-0012-0
发表时间：
2015
期刊：
Experimental & translational stroke medicine
影响因子：
--
作者：
Hong SH;Khoutorova L;Bazan NG;Belayev L
通讯作者：
Belayev L
影响因子：
6.9
作者：
Ansar, Saema;Chatzikonstantinou, Eva;Wistuba-Schier, Anja;Mirau-Weber, Silvia;Fatar, Marc;Hennerici, Michael G.;Meairs, Stephen
通讯作者：
Meairs, Stephen