Combined citicoline and docosahexaenoic acid treatment improves cognitive dysfunction following transient brain ischemia
Combined citicoline and docosahexaenoic acid treatment improves cognitive dysfunction following transient brain ischemia
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胞磷胆碱和二十二碳六烯酸联合治疗可改善短暂性脑缺血后的认知功能障碍
DOI：
10.1016/j.jphs.2019.02.003
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发表时间：
2019
影响因子：
3.5
通讯作者：
Fukunaga Kohji
中科院分区：
文献类型：
--
作者：
Nakazaki Eri;Yabuki Yasushi;Izumi Hisanao;Shinoda Yasuharu;Watanabe Fumiko;Hishida Yukihiro;Kamimura Ayako;Fukunaga Kohji
磷脂是细胞膜的结构组分，其在调节神经元膜功能和维持细胞内环境中作为各种信号传导途径的前体发挥重要作用。磷脂酰胆碱（PtdCho）是最丰富的细胞磷脂。胞磷胆碱和二十二碳六烯酸（DHA）是合成PtdCho的重要中间体。两种PtdCho中间体均在脑缺血中独立显示出神经保护作用，但它们的联合作用尚不清楚。本研究旨在使用20分钟双侧颈总动脉闭塞（BCCAO）小鼠模型研究口服胞磷胆碱和DHA治疗对改善脑缺血后认知缺陷的联合作用。用胞磷胆碱（40 mg/kg体重/天）和DHA（300 mg/kg体重/天）的组合或各自单独治疗BCCAO缺血小鼠总共11天。胞磷胆碱和DHA联合应用与单独应用相比，可显著提高缺血小鼠的学习记忆能力。此外，胞磷胆碱和DHA治疗显著防止神经元细胞死亡，并略微增加海马中含DHA的PtdCho，尽管不显著。总之，这些发现表明，联合胞磷胆碱和DHA治疗可能具有协同效益，部分改善短暂性脑缺血后的记忆缺陷。
Phospholipids are structural components of cellular membranes that play important roles as precursors for various signaling pathways in modulating neuronal membrane function and maintenance of the intracellular environment. Phosphatidylcholine (PtdCho) is the most abundant cellular phospholipid. Citicoline and docosahexaenoic acid (DHA) are essential intermediates in the synthesis of PtdCho. Both PtdCho intermediates have independently shown neuroprotective effects in cerebral ischemia, but their combined effect is unknown. This study aimed to investigate the combined effect of oral citicoline and DHA treatment on improvement of cognitive deficits following cerebral ischemia using a 20-min bilateral common carotid artery occlusion (BCCAO) mouse model. BCCAO ischemic mice were treated for a total of 11 days with a combination of citicoline (40 mg/kg body weight/day) and DHA (300 mg/kg body weight/day) or each alone. Combined citicoline and DHA synergistically and significantly improved learning and memory ability of ischemic mice compared with either alone. Further, citicoline and DHA treatment significantly prevented neuronal cell death, and slightly increased DHA-containing PtdCho in the hippocampus, albeit not significantly. Taken together, these findings suggest that combined citicoline and DHA treatment may have synergistic benefits for partially improving memory deficits following transient brain ischemia.