Promoting Neurovascular Recovery in Aged Mice after Ischemic Stroke - Prophylactic Effect of Omega-3 Polyunsaturated Fatty Acids.
Promoting Neurovascular Recovery in Aged Mice after Ischemic Stroke - Prophylactic Effect of Omega-3 Polyunsaturated Fatty Acids.
复制标题
促进老年小鼠缺血性中风后神经血管的恢复——Omega-3多不饱和脂肪酸的预防作用
DOI：
10.14336/ad.2017.0520
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发表时间：
2017-10
影响因子：
7.4
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Cai M;Zhang W;Weng Z;Stetler RA;Jiang X;Shi Y;Gao Y;Chen J
老年人群是缺血性卒中风险最高的人群之一，但大多数高龄（>80岁）卒中患者无法接受组织纤溶酶原激活剂溶栓治疗，这是FDA批准的唯一用于卒中患者的药物治疗。Omega-3多不饱和脂肪酸（n-3 PUFA）可显著减轻年轻成年啮齿动物的缺血性脑损伤，但尚未在老年动物中进行研究。这项研究调查了长期膳食补充n-3 PUFAs是否可以保护衰老的大脑免受脑缺血的影响，并改善长期的神经功能结局。在短暂性大脑中动脉闭塞（tMCAO）45分钟之前3个月和之后长达8周，每天向老年（18个月大）小鼠喂食富含n-3 PUFA的鱼油。在tMCAO后35天内通过圆柱试验和角落试验评估感觉运动结果，并在56天内通过免疫组织学评估脑修复动力学。小鼠接受饮食补充n-3 PUFA 3个月显示脑中n-3/n-6 PUFA含量的比率显著增加，并且显著减少tMCAO后的长期感觉运动缺陷和慢性缺血性脑组织损失。从机制上讲，n-3 PUFA强烈促进缺血后血管生成和神经发生，并增强tMCAO后的白色物质完整性。Pearson线性回归分析显示，tMCAO后神经发生和白色物质完整性的增强均与感觉运动活动的改善呈正相关。这项研究表明，预防性膳食补充n-3 PUFAs有效地改善了老年小鼠的长期卒中结局，可能是通过促进卒中后脑修复过程，如血管生成、神经发生和白色物质恢复。
The aged population is among the highest at risk for ischemic stroke, yet most stroke patients of advanced ages (>80 years) are excluded from access to thrombolytic treatment by tissue plasminogen activator, the only FDA approved pharmacological therapy for stroke victims. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) robustly alleviate ischemic brain injury in young adult rodents, but have not yet been studied in aged animals. This study investigated whether chronic dietary supplementation of n-3 PUFAs protects aging brain against cerebral ischemia and improves long-term neurological outcomes. Aged (18-month-old) mice were administered n-3 PUFA-enriched fish oil in daily chow for 3 months before and up to 8 weeks after 45 minutes of transient middle cerebral artery occlusion (tMCAO). Sensorimotor outcomes were assessed by cylinder test and corner test up to 35 days and brain repair dynamics evaluated immunohistologically up to 56 days after tMCAO. Mice receiving dietary supplementation of n-3 PUFAs for 3 months showed significant increases in brain ratio of n-3/n-6 PUFA contents, and markedly reduced long-term sensorimotor deficits and chronic ischemic brain tissue loss after tMCAO. Mechanistically, n-3 PUFAs robustly promoted post-ischemic angiogenesis and neurogenesis, and enhanced white matter integrity after tMCAO. The Pearson linear regression analysis revealed that the enhancement of neurogenesis and white matter integrity both correlated positively with improved sensorimotor activities after tMCAO. This study demonstrates that prophylactic dietary supplementation of n-3 PUFAs effectively improves long-term stroke outcomes in aged mice, perhaps by promoting post-stroke brain repair processes such as angiogenesis, neurogenesis, and white matter restoration.