Written by Joyce Smith, Staff Writer. Supplementation with omega-3 polyunsaturated fatty acids significantly increased brain ratio of n-3 to n-6 fatty acids, improved brain repair and protected against long-term brain injury.

Brain HealthStroke is a devastating neurological disease that offers no satisfactory therapies to preserve long-term neurological function. In a 2015 study 1, Zhang and his colleagues hypothesized that supplementing with omega-3 polyunsaturated fatty acids (n-3 PUFAs) would promote post-stroke recovery angiogenesis, neurogenesis, and oligodendrogenesis, thereby leading to long-term functional improvements. When young (4-month old) mice were given n-3 PUFA-enriched fish oil for three months before and up to one month after induced stroke, dietary n-3 PUFAs significantly increased levels of n-3 PUFAs in the brain and improved brain repair, as witnessed by improved long-term behavioral outcomes following their stroke. Specifically, n-3 PUFAs significantly improved angiogenesis and revascularization and boosted the survival of newborn neurons up to 35 days after stroke injury. Furthermore, there was significant post-stroke oligodendrogenesis (the formation of oligodrendites which are glial cells that protect the myelin sheaths of neurons) and remyelination, both of which supported white matter recovery (p≤0.05).

The same researchers then focused their attention on our elderly population. This population is among the highest at risk for ischemic stroke, suffers more severe neurological consequences and has a higher mortality rate; yet most older stroke patients (>80 years) do not have access to thrombolytic treatment using tissue plasminogen activator 2,3 (the only FDA approved pharmacological therapy for stroke victims) 3. Since n-3 PUFAs were able to significantly reduce ischemic brain injury in young mice, researchers querying n-3PUFAs effect on older populations investigated in a follow-up study 4 whether dietary n-3 PUFAs could protect the aging brain against ischemia stroke and improve stroke’s long-term neurological outcomes.

Three months prior to and up to eight weeks following an induced stroke (transient middle cerebral artery occlusion [tMCAO]), aged (18-month-old) mice were fed either chow enriched with n-3 PUFAs (N3H) or their daily chow with no added n-3 PUFAs (NHL). Sensory and motor nerve functions were assessed up to 35 days post tMCAO and immunohistological evaluation of brain repair was done up to 56 days post tMCAO. Researchers noted the following:

  • The ratio of brain n-3 to n-6 fatty acids increased significantly in N3H-fed mice (p≤0.05 vs N3L-fed mice), which aligns with previous studies4.
  • The N3H-fed mice showed significantly improved performance compared to mice fed the N3L diet (p≤0.05).
  • Dietary n-3 PUFAs supplementation protected against long-term behavioral deficits and stroke induced brain injury in the N3H-fed mice by stimulating angiogenesis and neurogenesis 1 (p≤0.05). They also reduced stroke-induced brain tissue loss and conferred long-term neuroprotection by increasing neural progenitor cells (p≤0.001) which positively correlated with sensorimotor recovery and decreased demyelination in the N3H-fed mice versus the N3L fed- mice (p≤0.01).

This study validates previous findings of n-3 PUFA-enriched fish oil’s ability to improve brain concentration of n-3 PUFAs and the n-3/n-6 ratio and, in addition, promote post-stroke brain repair such as angiogenesis, neurogenesis, and white matter restoration by providing long-term neurological and histological protection and survival in aged mice. From a clinical application perspective, prophylactic supplementation with n-3 PUFAs could potentially protect the brain against ischemic stroke as well as support recovery of neurological functions and prevent death after stroke-induced brain injury in our aged population.

Source: Zhang, Wenting, Hailian Wang, Hui Zhang, Rehana K. Leak, Yejie Shi, Xiaoming Hu, Yanqin Gao, and Jun Chen. “Dietary supplementation with omega-3 polyunsaturated fatty acids robustly promotes neurovascular restorative dynamics and improves neurological functions after stroke.” Experimental neurology 272 (2015): 170-180.

Source: Cai, Mengfei, Wenting Zhang, Zhongfang Weng, R. Anne Stetler, Xiaoyan Jiang, Yejie Shi, Yanqin Gao, and Jun Chen. “Promoting Neurovascular Recovery in Aged Mice after Ischemic Stroke-Prophylactic Effect of Omega-3 Polyunsaturated Fatty Acids.” Aging and disease 8, no. 5 (2017): 53

© 2017 Cai M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Posted February 26, 2018.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

References:

  1. Zhang W, Wang H, Zhang H, et al. Dietary supplementation with omega-3 polyunsaturated fatty acids robustly promotes neurovascular restorative dynamics and improves neurological functions after stroke. Experimental neurology. 2015;272:170-180.
  2. Arora R1 SE, Katz JM1, Cox M1, Saver JL2, Bhatt DL1, Fonarow GC1, Peterson ED1, Smith EE1, Schwamm LH1, Xian Y1, Libman RB1. Use and Outcomes of Intravenous Thrombolysis for Acute Ischemic Stroke in Patients ≥90 Years of Age. Stroke. 2016;47(9):2347-2354.
  3. Emberson J, Lees K, Lyden P, et al. Stroke Thrombolysis Trialists’ Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014;384(9958):1929-1935.
  4. Cai M, Zhang W, Weng Z, et al. Promoting Neurovascular Recovery in Aged Mice after Ischemic Stroke-Prophylactic Effect of Omega-3 Polyunsaturated Fatty Acids. Aging and disease. 2017;8(5):531.