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Aging and Disease    2017, Vol. 8 Issue (5) : 531-545     DOI: 10.14336/AD.2017.0520
Original Article |
Promoting Neurovascular Recovery in Aged Mice after Ischemic Stroke - Prophylactic Effect of Omega-3 Polyunsaturated Fatty Acids
Mengfei Cai1,Wenting Zhang1,*,Zhongfang Weng2,R. Anne Stetler1,2,3,Xiaoyan Jiang2,Yejie Shi2,3,Yanqin Gao1,2,*,Jun Chen1,2,3,*
1State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, and Collaborative Innovation Center, Fudan University, Shanghai 200032, China
2Pittsburgh Institute of Brain Disorders & Recovery and Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
3Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA 15261, USA
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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.

Keywords docosahexaenoic acid      eicosapentaenoic acid      angiogenesis      neurogenesis      white matter restoration     
Corresponding Authors: Wenting Zhang,Yanqin Gao,Jun Chen   
Issue Date: 01 October 2017
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Mengfei Cai
Wenting Zhang
Zhongfang Weng
R. Anne Stetler
Xiaoyan Jiang
Yejie Shi
Yanqin Gao
Jun Chen
Cite this article:   
Mengfei Cai,Wenting Zhang,Zhongfang Weng, et al. Promoting Neurovascular Recovery in Aged Mice after Ischemic Stroke - Prophylactic Effect of Omega-3 Polyunsaturated Fatty Acids[J]. A&D, 2017, 8(5): 531-545.
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