New Orleans, LA - Research conducted by a team of scientists from Columbia University College of Physicians and Surgeons and Dr. Nicolas Bazan, Boyd Professor and Director of the Neuroscience Center of Excellence at LSU Health Sciences Center New Orleans, found the novel use of a component of fish oil reduced brain trauma in newborn mice. The study reports that neonatal brain damage decreased by about 50% when a triglyceride lipid emulsion containing docosahexaenoic acid (DHA) was injected within two hours of the onset of ischemic stroke. The paper, n-3 Fatty Acid Rich Triglyceride Emulsions are Neuroprotective after Cerebral Hypoxic-Ischemic Injury in Neonatal Mice, is published in the journal, PLOS ONE, available online at http://dx.
The study compared the effectiveness of emulsions with two omega-3 fatty acids - DHA and eicosapentaenoic acid (EPA) - as well as optimal doses and therapeutic window. The researchers found that DHA provided protection while EPA did not. The therapeutic window ranged from 90 minutes prior to several hours after with the optimal window for treatment 0 - 2 hours. There was no protective effect at hour 4.
DHA is an essential omega-3-fatty acid and is vital for proper brain function. It is also necessary for the development of the nervous system, including vision. Moreover, omega-3 fatty acids, found in cold water fatty fish, including salmon, tuna, mackerel, sardines, shellfish, and herring, are part of a healthy diet that helps lower the risk of heart disease. DHA has potent anti-inflammatory effects. Since inflammation is at the root of many chronic diseases, DHA treatment has been widely demonstrated to have beneficial effects in patients with coronary heart disease, asthma, rheumatoid arthritis, osteoporosis, sepsis, cancer, dry eye disease, and age-related macular degeneration. Its potential benefit in stroke is now being documented.
EPA is also an omega-3 fatty acid found in coldwater fish. EPA can prevent the blood from clotting easily. Often paired with DHA in fish oil supplements, these fatty acids are known to reduce pain and swelling.
Ischemic strokes, representing about 87% of strokes, result from loss of blood flow to an area of the brain due to a blockage such as a clot or atherosclerosis. The damage includes an irreversibly injured core of tissue at the site of the blockage. The area of tissue surrounding the core, called the penumbra, is also damaged but potentially salvageable. The penumbra has a limited life span and appears to undergo irreversible damage within a few hours unless blood flow is reestablished and neuroprotective therapy is administered. A cascade of chemicals floods the tissue along with restored blood flow, including damaging free radicals and pro-inflammatory enzymes which can cause further damage and cell death.
Administering clot-busting drugs (thrombolysis) is currently the only treatment for ischemic stroke. But due to a narrow therapeutic window and complexity of administration, only 3-5% of patients typically benefit from thrombolysis.
Dr. Bazan's group at the LSU Health Sciences Center New Orleans Neuroscience Center of Excellence has increasingly shown that DHA is a potentially powerful treatment for stroke for nearly ten years. His study published in 2011 found DHA triggered production of Neuroprotectin D1 (NPD1), a naturally occurring neuroprotective molecule in the brain derived from DHA and discovered by Dr. Bazan. Not only did DHA treatment salvage stroke-damaged brain tissue that would have died, its repair mechanisms rendered some areas indistinguishable from normal tissue by 7 days.
"Stroke is a brain attack that each year kills 130,000 Americans," notes Dr. Bazan. "Strokes can occur at any age, including in newborns, with long-term and devastating consequences. DHA is already widely consumed as a dietary supplement in the US, and from a therapeutic point of view, we can now see a light at the end of the tunnel."
The researchers conclude that the findings suggest a need for further studies to determine if acute injection of these emulsions could be neuroprotective after stroke injury in humans. They also suggest that the emulsion rich in DHA will prove to be a novel and important therapy to treat stroke and could decrease mortality and increase long-term functional recovery after stroke in humans of different ages. The paper's senior author is Richard Deckelbaum, MD, director of the Institute of Human Nutrition at Columbia's College of Physicians & Surgeons.
According to the Centers for Disease Control and Prevention, 795,000 Americans have a stroke each year, and stroke causes 1 in every 18 deaths. Stroke is also a leading cause of long-term disability. Louisiana is among the states with the highest prevalence of stroke. It has been estimated that the direct and indirect costs of stroke in the United States totaled nearly $74 billion in 2010. In addition, with an estimated incidence of 1 in 2300 to 5000 births, stroke is more likely to occur in the perinatal period than at other times in childhood. Ischemic stroke in newborns is a disorder associated with significant long-term neurologic impairment. Twenty to 60% of survivors exhibit long-term detrimental neuropsychological consequences which include mental retardation, cerebral palsy, and behavioral disorders.
The research team also included Jill J. Williams, Korapat Mayurasakorn, and Vadim S. Ten at Columbia University; Susan J. Vannucci at Weill Cornell Medical College; and Christopher Mastropietro at Wayne State University.
The research was supported by grants from the National Institutes of Health.
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