Omega-3 fatty acids as a putative treatment for traumatic brain injury

Journal of Neurotrauma

Volumn 30, Issue 11, 2013, Pages 897-906

  Wang, Huan ^b   Hasadsri, Linda ^a   Wang, Bonnie H ^b   Lee, James V ^b   Erdman, John W ^c   Llano, Daniel A ^d   Barbey, Aron K ^b,c   Wszalek, Tracey ^c   Sharrock, Matthew F ^b  

^a MAYO CLINIC   (United States)

^b UNIVERSITY OF ILLINOIS   (United States)

^c UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^d UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

encephalopathy; omega 3 fatty acids; plasma membrane; therapeutic approaches to CNS injury; traumatic brain injury

Indexed keywords

DOCOSAHEXAENOIC ACID; ICOSAPENTAENOIC ACID;

ANTIOXIDANT ACTIVITY; DIET SUPPLEMENTATION; DRUG MECHANISM; FUNCTIONAL ASSESSMENT; HUMAN; IN VIVO STUDY; NEUROPROTECTION; NEUROTRANSMISSION; NONHUMAN; PATHOGENESIS; REVIEW; TRAUMATIC BRAIN INJURY; TREATMENT OUTCOME;

ANIMALS; BRAIN INJURIES; DIETARY SUPPLEMENTS; FATTY ACIDS, OMEGA-3; HUMANS;

EID: 84879959241     PISSN: 08977151     EISSN: 15579042     Source Type: Journal    
DOI: 10.1089/neu.2012.2672     Document Type: Review

References (190)

1. Warden D. (2006). Military TBI during the Iraq and Afghanistan wars. J Head Trauma Rehabil 21, 398-402
2. Langlois JA, Rutland-Brown W, and Wald MM. (2006). The epidemiology and impact of traumatic brain injury: A brief overview. J Head Trauma Rehabil 21, 375-378
3. Schroeder T, Irish C, Annest JL, Haileyesus T, Sarmiento K, and Mitchko J (2007). Nonfatal traumatic brain injuries from sports and recreation activities - United States, 2001-2005. Morbidity Mortality Weekly Rev Center for Disease Control and Prevention, p 733-737
4. Thurman DJ, Alverson C, Dunn KA, Guerrero J, and Sniezek JE. (1999). Traumatic brain injury in the United States: A public health perspective. J Head Trauma Rehabil 14, 602-615
5. Solomon GS, Ott SD, and Lovell MR. (2011). Long-term neurocognitive dysfunction in sports: What is the evidence? Clin Sports Med 30, 165-177
6. Omalu BI, DeKosky ST, Hamilton RL, et al. (2006). Chronic traumatic encephalopathy in a national football league player: Part II. Neurosurgery 59, 1086-1092; discussion 92-93
7. Guskiewicz KM, Marshall SW, Bailes J, et al. (2007). Recurrent concussion and risk of depression in retired professional football players. Med Sci Sports Exerc 39, 903-909
8. Omalu BI, Bailes J, Hammers JL, and Fitzsimmons RP. (2010 Chronic traumatic encephalopathy, suicides and parasuicides in professional American athletes: The role of the forensic pathologist. Am J Forensic Med Pathol 31, 130-132
9. Xiong Y, Mahmood A, and Chopp M. (2009). Emerging treatments for traumatic brain injury. Expert Opin Emerg Drugs 14, 67-84
10. Wu A, Ying Z, and Gomez-Pinilla F. (2008). Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience 155, 751-759
11. Lang-Lazdunski L, Blondeau N, Jarretou G, Lazdunski M, and Heurteaux C. (2003). Linolenic acid prevents neuronal cell death and paraplegia after transient spinal cord ischemia in rats. J Vasc Surg 38, 564-575
12. Wu A, Ying Z, and Gomez-Pinilla F. (2004). Dietary omega-3 fatty acids normalize BDNF levels, reduce oxidative damage, and counteract learning disability after traumatic brain injury in rats. J Neurotrauma 21, 1457-1467
13. Wu A, Ying Z, and Gomez-Pinilla F. (2011). The salutary effects of DHA dietary supplementation on cognition, neuroplasticity, and membrane homeostasis after brain trauma. J Neurotrauma 28, 2113-2122
14. Mills JD, Bailes JE, Sedney CL, Hutchins H, and Sears B. (2011 Omega-3 fatty acid supplementation and reduction of traumatic axonal injury in a rodent head injury model. J Neurosurg 114, 77-84
15. Mills JD, Hadley K, and Bailes JE. (2011). Dietary supplementation with the omega-3 fatty acid docosahexaenoic acid in traumatic brain injury. Neurosurgery 68, 474-481; discussion 481
16. Prins M. (2008). Diet, ketones, and neurotrauma. Epilepsia 49, 111-113
17. Shin SS, and Dixon CE. (2011). Oral fish oil restores striatal dopamine release after traumatic brain injury. Neurosci Lett 496, 168-171
18. Petraglia AL, Winkler EA, and Bailes JE. (2011). Stuck at the bench: Potential natural neuroprotective compounds for concussion. Surg Neurol Int 2, 146
19. National Research Council (2011). Nutrition and Traumatic Brain Injury: Improving Acute and Subacute Outcomes in Military Personnel. Erdman J, Oria M, Pillsbury L (eds.) Washington, D.C.: The National Academies Press, 2011
20. Kris-Etherton PM, Taylor DS, Yu-Poth S, et al. (2000). Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr 71, 179S-88S
21. Raper NR, Cronin FJ, and Exler J. (1992). Omega-3 fatty acid content of the US food supply. J Am Coll Nutr 11, 304-308
22. Innis SM. (2003). Perinatal biochemistry and physiology of longchain polyunsaturated fatty acids. J Pediatr 143, S1-8
23. Innis SM. (2007). Dietary (n-3) fatty acids and brain development. J Nutr 137, 855-859
24. Goyens PL, Spilker ME, Zock PL, Katan MB, and Mensink RP. (2006). Conversion of alpha-linolenic acid in humans is influenced by the absolute amounts of alpha-linolenic acid and linoleic acid in the diet and not by their ratio. Am J Clin Nutr 84, 44-53
25. Crawford MA. (1993). The role of essential fatty acids in neural development: Implications for perinatal nutrition. Am J Clin Nutr 57, 703S-09S; discussion 09S-10S
26. Singh M. (2005). Essential fatty acids, DHA and human brain. Indian J Pediatr 72, 239-242
27. Valentine RC, and Valentine DL. (2004). Omega-3 fatty acids in cellular membranes: A unified concept. Prog Lipid Res 43, 383-402
28. Hering H, Lin CC, and Sheng M. (2003). Lipid rafts in the maintenance of synapses, dendritic spines, and surface AMPA receptor stability. J Neurosci 23, 3262-3271
29. Innis SM. (2008). Dietary omega 3 fatty acids and the developing brain. Brain Res 1237, 35-43
30. Tsui-Pierchala BA, Encinas M, Milbrandt J, and Johnson EM, Jr. (2002). Lipid rafts in neuronal signaling and function. Trends Neurosci 25, 412-417
31. Stillwell W, and Wassall SR. (2003). Docosahexaenoic acid: Membrane properties of a unique fatty acid. Chem Phys Lipids 126, 1-27
32. Armstrong VT, Brzustowicz MR, Wassall SR, Jenski LJ, and Stillwell W. (2003). Rapid flip-flop in polyunsaturated (docosahexaenoate) phospholipid membranes. Arch Biochem Biophys 414, 74-82
33. Chapkin RS, Wang N, Fan YY, Lupton JR, and Prior IA. (2008 Docosahexaenoic acid alters the size and distribution of cell surface microdomains. Biochim Biophys Acta 1778, 466-471
34. Ehringer W, Belcher D, Wassall SR, and Stillwell W. (1990). A comparison of the effects of linolenic (18:3 omega 3) and docosahexaenoic (22:6 omega 3) acids on phospholipid bilayers. Chem Phys Lipids 54, 79-88
35. Huster D, Arnold K, and Gawrisch K. (1998). Influence of docosahexaenoic acid and cholesterol on lateral lipid organization in phospholipid mixtures. Biochemistry 37, 17299-17308
36. Kafrawy O, Zerouga M, Stillwell W, and Jenski LJ. (1998). Docosahexaenoic acid in phosphatidylcholine mediates cytotoxicity more effectively than other omega-3 and omega-6 fatty acids. Cancer Lett 132, 23-29
37. Salem N, Jr., and Niebylski CD. (1995). The nervous system has an absolute molecular species requirement for proper function. Mol Membr Biol 12, 131-134
38. Smaby JM, Momsen MM, Brockman HL, and Brown RE. (1997 Phosphatidylcholine acyl unsaturation modulates the decrease in interfacial elasticity induced by cholesterol. Biophys J 73, 1492-1505
39. Wassall SR, and Stillwell W. (2008). Docosahexaenoic acid domains: The ultimate non-raft membrane domain. Chem Phys Lipids 153, 57-63
40. Stillwell W, Shaikh SR, Zerouga M, Siddiqui R, and Wassall SR. (2005). Docosahexaenoic acid affects cell signaling by altering lipid rafts. Reprod Nutr Dev 45, 559-579
41. Shaikh SR, Cherezov V, Caffrey M, Stillwell W, and Wassall SR (2003). Interaction of cholesterol with a docosahexaenoic acidcontaining phosphatidylethanolamine: Trigger for microdomain/raft formation? Biochemistry 42, 12028-12037
42. Wurtman RJ. (2008). Synapse formation and cognitive brain development: Effect of docosahexaenoic acid and other dietary constituents. Metabolism 57, S6-10
43. Seebungkert B, and Lynch JW. (2002). Effects of polyunsaturated fatty acids on voltage-gated K+ and Na + channels in rat olfactory receptor neurons. Eur J Neurosci 16, 2085-2094
44. Xiao Y, and Li X. (1999). Polyunsaturated fatty acids modify mouse hippocampal neuronal excitability during excitotoxic or convulsant stimulation. Brain Res 846, 112-121
45. Turner N, Else PL, and Hulbert AJ. (2003). Docosahexaenoic acid (DHA) content of membranes determines molecular activity of the sodium pump: Implications for disease states and metabolism. Naturwissenschaften 90, 521-523
46. Bazan NG. (2005). Neuroprotectin D1 (NPD1): A DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress. Brain Pathol 15, 159-166
47. Bazan NG, Musto AE, and Knott EJ. (2011). Endogenous signaling by omega-3 docosahexaenoic acid-derived mediators sustains homeostatic synaptic and circuitry integrity. Mol Neurobiol 44, 216-222
48. Niemoller TD, Stark DT, and Bazan NG. (2009). Omega-3 fatty acid docosahexaenoic acid is the precursor of neuroprotectin D1 in the nervous system. World Rev Nutr Diet 99, 46-54
49. Weylandt KH, Chiu CY, Gomolka B, Waechter SF, and Wiedenmann B. (2012). Omega-3 fatty acids and their lipid mediators: Towards an understanding of resolvin and protectin formation. Prostaglandins Other Lipid Mediat 97, 73-82
50. Tassoni D, Kaur G, Weisinger RS, and Sinclair AJ. (2008). The role of eicosanoids in the brain. Asia Pac J Clin Nutr 17, 220-228
51. Im DS. (2012). Omega-3 fatty acids in anti-inflammation (proresolution) and GPCRs. Prog Lipid Res 51, 232-237
52. Horrocks LA, and Farooqui AA. (2004). Docosahexaenoic acid in the diet: Its importance in maintenance and restoration of neural membrane function. Prostaglandins Leukot Essent Fatty Acids 70, 361-372
53. Kitajka K, Puskas LG, Zvara A, et al (2002). The role of n-3 polyunsaturated fatty acids in brain: Modulation of rat brain gene expression by dietary n-3 fatty acids. Proc Natl Acad Sci USA 99, 2619-2624
54. Lengqvist J, Mata De Urquiza A, Bergman AC, et al. (2004 Polyunsaturated fatty acids including docosahexaenoic and arachidonic acid bind to the retinoid X receptor alpha ligand-binding domain. Mol Cell Proteomics 3, 692-703
55. Rioux L, and Arnold SE. (2005). The expression of retinoic acid receptor alpha is increased in the granule cells of the dentate gyrus in schizophrenia. Psychiatry Res 133, 13-21
56. Lane MA, and Bailey SJ. (2005). Role of retinoid signalling in the adult brain. Prog Neurobiol 75, 275-293
57. Ahmad A, Moriguchi T, and Salem N. (2002). Decrease in neuron size in docosahexaenoic acid-deficient brain. Pediatr Neurol 26, 210-218
58. Aid S, Vancassel S, Poumes-Ballihaut C, Chalon S, Guesnet P, and Lavialle M. (2003). Effect of a diet-induced n-3 PUFA depletion on cholinergic parameters in the rat hippocampus. J Lipid Res 44, 1545-1551
59. Chalon S. (2006). Omega-3 fatty acids and monoamine neurotransmission. Prostaglandins Leukot Essent Fatty Acids 75, 259-269
60. Innis SM, Gilley J, and Werker J (2001). Are human milk long-chain polyunsaturated fatty acids related to visual and neural development in breast-fed term infants? J Pediatr 139, 532-538
61. Wainwright RE, Bulman-Fleming MB, Lévesque S, Mutsaers L, and McCutcheon D. (1998). A saturated-fat diet during development alters dendritic growth in mouse brain. Nutr Neurosci 1, 49-58
62. He C, Qu X, Cui L, Wang J, and Kang JX. (2009). Improved spatial learning performance of fat-1 mice is associated with enhanced neurogenesis and neuritogenesis by docosahexaenoic acid. Proc Natl Acad Sci USA 106, 11370-11375
63. Farkas E, de Wilde MC, Kiliaan AJ, Meijer J, Keijser JN, and Luiten PG. (2002). Dietary long chain PUFAs differentially affect hippocampal muscarinic 1 and serotonergic 1A receptors in experimental cerebral hypoperfusion. Brain Res 954, 32-41
64. Farkas E, de Wilde MC, Kiliaan AJ, and Luiten PG. (2002). Systemic effects of dietary n-3 PUFA supplementation accompany changes of CNS parameters in cerebral hypoperfusion. Ann NY Acad Sci 977, 77-86
65. Catalan J, Moriguchi T, Slotnick B, Murthy M, Greiner RS, and Salem N, Jr. (2002). Cognitive deficits in docosahexaenoic aciddeficient rats. Behav Neurosci 116, 1022-1031
66. Bourre JM, Francois M, Youyou A, et al. (1989). The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. J Nutr 119, 1880-1892
67. Carrie I, Clement M, de Javel D, Frances H, and Bourre JM. (2000 Phospholipid supplementation reverses behavioral and biochemical alterations induced by n-3 polyunsaturated fatty acid deficiency in mice. J Lipid Res 41, 473-480
68. Yamamoto N, Hashimoto A, Takemoto Y, et al. (1988). Effect of the dietary alpha-linolenate/linoleate balance on lipid compositions and learning ability of rats. II. Discrimination process, extinction process, and glycolipid compositions. J Lipid Res 29, 1013-1021
69. Blokland A (1995). Acetylcholine: A neurotransmitter for learning and memory? Brain Res Brain Res Rev 21, 285-300
70. Everitt BJ, and Robbins TW. (1997). Central cholinergic systems and cognition. Annu Rev Psychol 48, 649-684
71. Fadda F, Cocco S, and Stancampiano R. (2000). Hippocampal acetylcholine release correlates with spatial learning performance in freely moving rats. Neuroreport 11, 2265-2269
72. Himmelheber AM, Sarter M, and Bruno JP. (2000). Increases in cortical acetylcholine release during sustained attention performance in rats. Brain Res Cogn Brain Res 9, 313-325
73. Passetti F, Dalley JW, O'Connell MT, Everitt BJ, and Robbins TW. (2000). Increased acetylcholine release in the rat medial prefrontal cortex during performance of a visual attentional task. Eur J Neurosci 12, 3051-3058
74. Chalon S, Vancassel S, Zimmer L, Guilloteau D, and Durand G. (2001). Polyunsaturated fatty acids and cerebral function: Focus on monoaminergic neurotransmission. Lipids 36, 937-944
75. Delion S, Chalon S, Guilloteau D, Besnard JC, and Durand G. (1996). alpha-Linolenic acid dietary deficiency alters age-related changes of dopaminergic and serotoninergic neurotransmission in the rat frontal cortex. J Neurochem 66, 1582-1591
76. Zimmer L, Delion-Vancassel S, Durand G, et al. (2000). Modification of dopamine neurotransmission in the nucleus accumbens of rats deficient in n-3 polyunsaturated fatty acids. J Lipid Res 41, 32-40
77. Zimmer L, Vancassel S, Cantagrel S, et al. (2002). The dopamine mesocorticolimbic pathway is affected by deficiency in n-3 polyunsaturated fatty acids. Am J Clin Nutr 75, 662-667
78. Mathe JM, Nomikos GG, Blakeman KH, and Svensson TH. (1999 Differential actions of dizocilpine (MK-801) on the mesolimbic and mesocortical dopamine systems: Role of neuronal activity. Neuropharmacology 38, 121-128
79. Zimmer L, Delpal S, Guilloteau D, Aioun J, Durand G, and Chalon S. (2000). Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex. Neurosci Lett 284, 25-28
80. Brenna JT, and Diau GY. (2007). The influence of dietary docosahexaenoic acid and arachidonic acid on central nervous system polyunsaturated fatty acid composition. Prostaglandins Leukot Essent Fatty Acids 77, 247-250
81. Diau GY, Hsieh AT, Sarkadi-Nagy EA, Wijendran V, Nathanielsz PW, and Brenna JT. (2005). The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system. BMC Med 3:11
82. Bailes JE, and Mills JD. (2010). Docosahexaenoic acid reduces traumatic axonal injury in a rodent head injury model. J Neurotrauma 27, 1617-1624
83. Pan HC, Kao TK, Ou YC, et al. (2009). Protective effect of docosahexaenoic acid against brain injury in ischemic rats. J Nutr Biochem 20, 715-725
84. Suchy J, Chan A, and Shea TB. (2009). Dietary supplementation with a combination of alpha-lipoic acid, acetyl-L-carnitine, glycerophosphocoline, docosahexaenoic acid, and phosphatidylserine reduces oxidative damage to murine brain and improves cognitive performance. Nutr Res 29, 70-74
85. Choi-Kwon S, Park KA, Lee HJ, et al. (2004). Temporal changes in cerebral antioxidant enzyme activities after ischemia and reperfusion in a rat focal brain ischemia model: Effect of dietary fish oil. Brain Res Dev Brain Res 152, 11-18
86. Glozman S, Green P, and Yavin E. (1998). Intraamniotic ethyl docosahexaenoate administration protects fetal rat brain from ischemic stress. J Neurochem 70, 2484-2491
87. Belayev L, Marcheselli VL, Khoutorova L, et al. (2005). Docosahexaenoic acid complexed to albumin elicits high-grade ischemic neuroprotection. Stroke 36, 118-123
88. Huang WL, King VR, Curran OE, et al. (2007). A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury. Brain 130, 3004-3019
89. King VR, Huang WL, Dyall SC, Curran OE, Priestley JV, and Michael-Titus AT. (2006). Omega-3 fatty acids improve recovery, whereas omega-6 fatty acids worsen outcome, after spinal cord injury in the adult rat. J Neurosci 26, 4672-4680
90. Effect of docosahexaenoic acid, an omega-3 polyunsaturated fatty acid, in a mouse facial nerve injury model. British Pharmacological Society 75th Anniversary Meeting; 2006. Proceedings of the British Pharmacological Society
91. Gladman SJ, Huang W, Lim SN, et al. (2012). Improved outcome after peripheral nerve injury in mice with increased levels of endogenous omega-3 polyunsaturated fatty acids. J Neurosci 32, 563-571
92. Bazan NG, Molina MF, and Gordon WC. (2011). Docosahexaenoic acid signalolipidomics in nutrition: Significance in aging, neuroinflammation, macular degeneration, Alzheimer's, and other neurodegenerative diseases. Annu Rev Nutr 31, 321-351
93. Yurko-Mauro K, McCarthy D, Rom D, et al. (2010). Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement 6, 456-464
94. Bistrian BR, Askew W, Erdman JW, Jr., and Oria MP. (2011). Nutrition and traumatic brain injury: A perspective from the Institute of Medicine report. JPEN J Parenter Enteral Nutr 35, 556-9
95. Garbagnati F, Cairella G, De Martino A, et al. (2009). Is antioxidant and n-3 supplementation able to improve functional status in poststroke patients? Results from the Nutristroke Trial. Cerebrovasc Dis 27, 375-383
96. Poppitt SD, Howe CA, Lithander FE, et al. (2009). Effects of moderate-dose omega-3 fish oil on cardiovascular risk factors and mood after ischemic stroke: A randomized, controlled trial. Stroke 40, 3485-3492
97. Yoneda H, Shirao S, Kurokawa T, Fujisawa H, Kato S, and Suzuki M. (2008). Does eicosapentaenoic acid (EPA) inhibit cerebral vasospasm in patients after aneurysmal subarachnoid hemorrhage? Acta Neurol Scand 118, 54-59
98. Skerrett PJ, and Hennekens CH. (2003). Consumption of fish and fish oils and decreased risk of stroke. Prev Cardiol 6, 38-41
99. He K, Rimm EB, Merchant A, et al. (2002). Fish consumption and risk of stroke in men. JAMA 288, 3130-3136
100. Iso H, Rexrode KM, Stampfer MJ, et al. (2001). Intake of fish and omega-3 fatty acids and risk of stroke in women. JAMA 285, 304-312
101. Lalancette-Hebert M, Julien C, Cordeau P, et al. (2011). Accumulation of dietary docosahexaenoic acid in the brain attenuates acute immune response and development of postischemic neuronal damage. Stroke 42, 2903-2909
102. Mozaffarian D, Longstreth WT, Jr., Lemaitre RN, et al. (2005). Fish consumption and stroke risk in elderly individuals: The cardiovascular health study. Arch Intern Med 165, 200-206
103. Dirnagl U, Iadecola C, and Moskowitz MA. (1999). Pathobiology of ischaemic stroke: An integrated view. Trends Neurosci 22, 391-397
104. Moskowitz MA, Lo EH, and Iadecola C. (2010). The science of stroke: Mechanisms in search of treatments. Neuron 67, 181-198
105. Mukherjee PK, Marcheselli VL, Serhan CN, and Bazan NG. (2004 Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci USA 101, 8491-8496
106. Bazan NG. (2009). Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's disease. J Lipid Res 50, S400-405
107. Marcheselli VL, Hong S, Lukiw WJ, et al. (2003). Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 278, 43807-43817
108. Cao DH, Xu JF, Xue RH, Zheng WF, and Liu ZL. (2004). Protective effect of chronic ethyl docosahexaenoate administration on brain injury in ischemic gerbils. Pharmacol Biochem Behav 79, 651-659
109. Green P, Glozman S, Weiner L, and Yavin E. (2001). Enhanced free radical scavenging and decreased lipid peroxidation in the rat fetal brain after treatment with ethyl docosahexaenoate. Biochim Biophys Acta 1532, 203-212
110. Okada M, Amamoto T, Tomonaga M, et al. (1996). The chronic administration of docosahexaenoic acid reduces the spatial cognitive deficit following transient forebrain ischemia in rats. Neuroscience 71, 17-25
111. Farooqui AA. (2010). Potential neuroprotective strategies for traumatic brain injury. In: Neurochemical Aspects of Neurotraumatic and Neurodegenerative Diseases. 1st ed: Springer, pp. 219-248
112. Dyall SC, and Michael-Titus AT. (2008). Neurological benefits of omega-3 fatty acids. Neuromolecular Med 10, 219-235
113. Farooqui AA, Horrocks LA, and Farooqui T. (2007). Modulation of inflammation in brain: A matter of fat. J Neurochem 101, 577-599
114. Bazan NG. (2006). Cell survival matters: Docosahexaenoic acid signaling, neuroprotection and photoreceptors. Trends Neurosci 29, 263-271
115. Artal-Sanz M, and Tavernarakis N. (2005). Proteolytic mechanisms in necrotic cell death and neurodegeneration. FEBS Lett 579, 3287-3296
116. Choi DW, and Rothman SM. (1990). The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci 13, 171-182
117. Obrenovitch TP, and Urenjak J (1997). Is high extracellular glutamate the key to excitotoxicity in traumatic brain injury? J Neurotrauma 14, 677-698
118. Wang X, Zhao X, Mao ZY, Wang XM, and Liu ZL. (2003). Neuroprotective effect of docosahexaenoic acid on glutamate-induced cytotoxicity in rat hippocampal cultures. Neuroreport 14, 2457-2461
119. Menard C, Patenaude C, Gagne AM, and Massicotte G. (2009 AMPA receptor-mediated cell death is reduced by docosahexaenoic acid but not by eicosapentaenoic acid in area CA1 of hippocampal slice cultures. J Neurosci Res 87, 876-886
120. Pratico D, Reiss P, Tang LX, Sung S, Rokach J, and McIntosh TK. (2002). Local and systemic increase in lipid peroxidation after moderate experimental traumatic brain injury. J Neurochem 80, 894-898
121. Hall ED, and Springer JE. (2004). Neuroprotection and acute spinal cord injury: A reappraisal. NeuroRx 1, 80-100
122. Xu W, Chi L, Xu R, et al. (2005). Increased production of reactive oxygen species contributes to motor neuron death in a compression mouse model of spinal cord injury. Spinal Cord 43, 204-213
123. Loane DJ, and Faden AI. (2010). Neuroprotection for traumatic brain injury: Translational challenges and emerging therapeutic strategies. Trends Pharmacol Sci 31, 596-604
124. Ikonomidou C, and Turski L (2002). Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol 1, 383-386
125. Maas AI, Murray G, Henney H, 3rd, et al. (2006). Efficacy and safety of dexanabinol in severe traumatic brain injury: Results of a phase III randomised, placebo-controlled, clinical trial. Lancet Neurol 5, 38-45
126. Narayan RK, Michel ME, Ansell B, et al. (2002). Clinical trials in head injury. J Neurotrauma 19, 503-557
127. Alderson P, and Roberts I. (2005). Corticosteroids for acute traumatic brain injury. Cochrane Database Syst Rev(1):CD000196
128. Wright DW, Kellermann AL, Hertzberg VS, et al. (2007). ProTECT: A randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med 49, 391-402, 02 e1-2
129. Xiao G, Wei J, Yan W, Wang W, and Lu Z. (2008). Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: A randomized controlled trial. Crit Care 12, R61
130. Wible EF, and Laskowitz DT. (2010). Statins in traumatic brain injury. Neurotherapeutics 7, 62-73
131. Davidson MH, Stein EA, Bays HE, et al. (2007). Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: An 8-week, randomized, double-blind, placebo-controlled study. Clin Ther 29, 1354-1367
132. Wohl DA, Tien HC, Busby M, et al. (2005). Randomized study of the safety and efficacy of fish oil (omega-3 fatty acid) supplementation with dietary and exercise counseling for the treatment of antiretroviral therapy-associated hypertriglyceridemia. Clin Infect Dis 41, 1498-1504
133. Ott J, Hiesgen C, and Mayer K. (2011). Lipids in critical care medicine. Prostaglandins Leukot Essent Fatty Acids 85, 267-273
134. Rapoport SI, Rao JS, and Igarashi M. (2007). Brain metabolism of nutritionally essential polyunsaturated fatty acids depends on both the diet and the liver. Prostaglandins Leukot Essent Fatty Acids 77, 251-261
135. Substances affirmed as generally recognized as safe: Menhaden oil. Final Rule: Federal Registry, 1997, 30751-30757
136. Kris-Etherton PM, Harris WS, and Appel LJ. (2003). Omega-3 fatty acids and cardiovascular disease: New recommendations from the American Heart Association. Arterioscler Thromb Vasc Biol 23, 151-152
137. Lien EL. (2009). Toxicology and safety of DHA. Prostaglandins Leukot Essent Fatty Acids 81, 125-132
138. Pedersen HS, Mulvad G, Seidelin KN, Malcom GT, and Boudreau DA. (1999). N-3 fatty acids as a risk factor for haemorrhagic stroke. Lancet 353, 812-813
139. Bender NK, Kraynak MA, Chiquette E, Linn WD, Clark GM, and Bussey HI. (1998). Effects of marine fish oils on the anticoagulation status of patients receiving chronic warfarin therapy. J Thromb Thrombolysis 5, 257-261
140. Eritsland J, Arnesen H, Gronseth K, Fjeld NB, and Abdelnoor M. (1996). Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Am J Cardiol 77, 31-36
141. Leaf A, Jorgensen MB, Jacobs AK, et al (1994). Do fish oils prevent restenosis after coronary angioplasty? Circulation 90, 2248-2257
142. Woodman RJ, Mori TA, Burke V, et al. (2003). Effects of purified eicosapentaenoic acid and docosahexaenoic acid on platelet, fibrinolytic and vascular function in hypertensive type 2 diabetic patients. Atherosclerosis 166, 85-93
143. Bays HE. (2007). Safety considerations with omega-3 fatty acid therapy. Am J Cardiol 99, 35C-43C
144. Calo L, Bianconi L, Colivicchi F, et al. (2005). N-3 Fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: A randomized, controlled trial. J Am Coll Cardiol 45, 1723-1728
145. Covington MB. (2004). Omega-3 fatty acids. Am Fam Physician 70, 133-140
146. Kris-Etherton PM, Harris WS, and Appel LJ. (2003). Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler Thromb Vasc Biol 23, e20-30
147. Cosgrove JP, Church DF, and Pryor WA. (1987). The kinetics of the autoxidation of polyunsaturated fatty acids. Lipids 22, 299-304
148. Guillen MD, and Goicoechea E. (2008). Toxic oxygenated alpha, beta-unsaturated aldehydes and their study in foods: A review. Crit Rev Food Sci Nutr 48, 119-136
149. Calzada C, Colas R, Guillot N, et al. (2010). Subgram daily supplementation with docosahexaenoic acid protects low-density lipoproteins from oxidation in healthy men. Atherosclerosis 208, 467-472
150. Mori TA, Woodman RJ, Burke V, Puddey IB, Croft KD, and Beilin LJ. (2003). Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Free Radic Biol Med 35, 772-781
151. Wu WH, Lu SC, Wang TF, Jou HJ, and Wang TA. (2006). Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women. Eur J Clin Nutr 60, 386-92
152. Arisawa K, Matsumura T, Tohyama C, et al. (2003). Fish intake, plasma omega-3 polyunsaturated fatty acids, and polychlorinated dibenzo-p-dioxins/ polychlorinated dibenzo-furans and co-planar polychlorinated biphenyls in the blood of the Japanese population. Int Arch Occup Environ Health 76, 205-215
153. Mulvad G, Pedersen HS, Hansen JC, et al. (1996). The Inuit diet. Fatty acids and antioxidants, their role in ischemic heart disease, and exposure to organochlorines and heavy metals. An international study. Arctic Med Res 55, 20-24
154. Mozaffarian D, and Rimm EB. (2006). Fish intake, contaminants, and human health: Evaluating the risks and the benefits. JAMA 296, 1885-1899
155. Foran SE, Flood JG, and Lewandrowski KB. (2003). Measurement of mercury levels in concentrated over-the-counter fish oil preparations: Is fish oil healthier than fish? Arch Pathol Lab Med 127, 1603-1605
156. Kew S, Mesa MD, Tricon S, Buckley R, Minihane AM, and Yaqoob P. (2004). Effects of oils rich in eicosapentaenoic and docosahexaenoic acids on immune cell composition and function in healthy humans. Am J Clin Nutr 79, 674-681
157. Kelley DS, Taylor PC, Nelson GJ, and Mackey BE. (1998). Dietary docosahexaenoic acid and immunocompetence in young healthy men. Lipids 33, 559-566
158. Kelley DS, Taylor PC, Nelson GJ, et al. (1999). Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids 34, 317-324
159. Sydenham E, Dangour AD, and Lim WS. (2012). Omega 3 fatty acid for the prevention of cognitive decline and dementia. Cochrane Database Syst Rev 6:CD005379
160. Bays H. (2007). Fish oil composition of Omacor and the GISSI trial. Am J Cardiol 99, 1483-1484
161. Kotani S, Sakaguchi E, Warashina S, et al. (2006). Dietary supplementation of arachidonic and docosahexaenoic acids improves cognitive dysfunction. Neurosci Res 56, 159-164
162. Blyth BJ, Farahvar A, He H, et al. (2011). Elevated serum ubiquitin carboxy-terminal hydrolase L1 is associated with abnormal bloodbrain barrier function after traumatic brain injury. J Neurotrauma 28, 2453-2462
163. Kochanek PM, Berger RP, Bayir H, Wagner AK, Jenkins LW, and Clark RS. (2008). Biomarkers of primary and evolving damage in traumatic and ischemic brain injury: Diagnosis, prognosis, probing mechanisms, and therapeutic decision making. Curr Opin Crit Care 14, 135-141
164. Mehta SS. (2010). Biochemical serum markers in head injury: An emphasis on clinical utility. Clin Neurosurg 57, 134-140
165. Topolovec-Vranic J, Pollmann-Mudryj MA, Ouchterlony D, et al. (2011). The value of serum biomarkers in prediction models of outcome after mild traumatic brain injury. J Trauma 71, S478-486
166. Muller K, Townend W, Biasca N, et al. (2007). S100B serum level predicts computed tomography findings after minor head injury. J Trauma 62, 1452-1456
167. Hodge J, Sanders K, and Sinclair AJ. (1993). Differential utilization of eicosapentaenoic acid and docosahexaenoic acid in human plasma. Lipids 28, 525-531
168. Innis SM. (1992). Plasma and red blood cell fatty acid values as indexes of essential fatty acids in the developing organs of infants fed with milk or formulas. J Pediatr 120, S78-86
169. Spector AA. (2001). Plasma free fatty acid and lipoproteins as sources of polyunsaturated fatty acid for the brain. J Mol Neurosci 16, 159-165; discussion 215-221
170. Carver JD, Benford VJ, Han B, and Cantor AB. (2001). The relationship between age and the fatty acid composition of cerebral cortex and erythrocytes in human subjects. Brain Res Bull 56, 79-85
171. Bouwstra H, Dijck-Brouwer DA, Wildeman JA, et al. (2003). Longchain polyunsaturated fatty acids have a positive effect on the quality of general movements of healthy term infants. Am J Clin Nutr 78, 313-318
172. Dunstan JA, Simmer K, Dixon G, and Prescott SL. (2008). Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: A randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 93, F45-50
173. Helland IB, Smith L, Saarem K, Saugstad OD, and Drevon CA (2003). Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Pediatrics 111, e39-44
174. Hibbeln JR, Davis JM, Steer C, et al. (2007). Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): An observational cohort study. Lancet 369, 578-585
175. Innis SM, and Friesen RW. (2008). Essential n-3 fatty acids in pregnant women and early visual acuity maturation in term infants. Am J Clin Nutr 87, 548-557
176. Oken E, Wright RO, Kleinman KP, et al. (2005). Maternal fish consumption, hair mercury, and infant cognition in a U.S. Cohort. Environ Health Perspect 113, 1376-1380
177. Uauy R, and Dangour AD. (2006). Nutrition in brain development and aging: Role of essential fatty acids. Nutr Rev 64, S24-33; discussion S72-91
178. Williams C, Birch EE, Emmett PM, and Northstone K. (2001 Stereoacuity at age 3.5 y in children born full-term is associated with prenatal and postnatal dietary factors: A report from a populationbased cohort study. Am J Clin Nutr 73, 316-322
179. Dullemeijer C, Durga J, Brouwer IA, et al. (2007). n-3 Fatty acid proportions in plasma and cognitive performance in older adults. Am J Clin Nutr 86, 1479-1485
180. Kalmijn S, van Boxtel MP, Ocke M, Verschuren WM, Kromhout D, and Launer LJ. (2004). Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology 62, 275-280
181. Morris MC, Evans DA, Bienias JL, et al. (2003). Dietary fats and the risk of incident Alzheimer disease. Arch Neurol 60, 194-200
182. Nurk E, Drevon CA, Refsum H, et al. (2007). Cognitive performance among the elderly and dietary fish intake: The Hordaland Health Study. Am J Clin Nutr 86, 1470-1478
183. Schaefer EJ, Bongard V, Beiser AS, et al. (2006). Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: The Framingham Heart Study. Arch Neurol 63, 1545-1550
184. van Gelder BM, Tijhuis M, Kalmijn S, and Kromhout D. (2007). Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men: The Zutphen Elderly Study. Am J Clin Nutr 85, 1142-1147
185. Bazan NG. (1970). Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain. Biochim Biophys Acta 218, 1-10
186. Neuringer M, Anderson GJ, and Connor WE. (1988). The essentiality of n-3 fatty acids for the development and function of the retina and brain. Annu Rev Nutr 8, 517-541
187. Kim HY, Akbar M, Lau A, and Edsall L. (2000). Inhibition of neuronal apoptosis by docosahexaenoic acid (22:6n-3). Role of phosphatidylserine in antiapoptotic effect. J Biol Chem 275, 35215-35223
188. Lewis M, Ghassemi P, and Hibbeln J. (2013). Therapeutic use of omega-3 fatty acids in severe head trauma. Am J Emerg Med 31, 273
189. Roberts L, Bailes J, Dedhia H, et al. (2008). Surviving a mine explosion. J Am Coll Surg 207, 276-283
190. Tur JA, Bibiloni MM, Sureda A, and Pons A. (2012). Dietary sources of omega 3 fatty acids: Public health risks and benefits. Br J Nutr 107, S23-52