Lipids

, Volume 38, Issue 4, pp 303–315 | Cite as

The potential role for arachidonic and docosahexaenoic acids in protection against some central nervous system injuries in preterm infants

  • M. A. Crawford
  • I. Golfetto
  • K. Ghebremeskel
  • Y. Min
  • T. Moodley
  • L. Poston
  • A. Phylactos
  • S. Cunnane
  • W. Schmidt
Articles

Abstract

The risk of central nervous, visual, and auditory damage increases from 2/1000 live births in the normal birthweight to >200/1000 as birthweight falls below 1500 g. Such babies are most likely to be born preterm. Advances in infant care have led to increasing numbers of very-low-birthweight, preterm infants surviving to school age with moderate to severe brain damage. Steroids are one of the current treatments, but they cause significant, long-term problems. The evidence reported here suggests an additional approach to protecting the very preterm infant by supporting neurovascular membrane integrity. The complications of preterm, very-low-birthweight babies include bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, and necrotizing enterocolitis, all of which have a vascular component. Arachidonic acid (AA) and DHA are essential, structural, and functional constituents of cell membranes. They are especially required for the growth and function of the brain and vascular systems, which are the primary biofocus of human fetal growth. Molecular dynamics and experimental evidence suggest that DHA could be the ligand for the retinoid X receptor (RXR) in neural tissue. RXR activation is an obligatory step in signaling to the nucleus and in the regulation of gene expression. Very preterm babies are born with minimal fat stores and suboptimal circulating levels of these nutrients. Postanatally, they lose the biomagnification of the proportions of AA and DHA by the placenta for the fetus. No current nutritional management repairs these deficits. The placental biomagnification profile highlights AA rather than DHA. The resultant fetal FA profile closely resembles that of the vascular endothelium and not the brain. Without this nourishment, cell membrane abnormalities would be predicted. We present a scientific rationale for a common pathogenic process in the complications of prematurity.

Abbreviations

AA

arachidonic acid

ACh

acetyl choline

BPD

bronchopulmonary dysplasia

CI

confidence interval

CPG

choline phosphoglycerides

EPG

ethanolamine phosphoglycerides

IL

interleukin

IVH

intraventricular hemorrhage

LA

linoleic acid

MRI

magnetic resonance imaging

NEC

necrotizing enterocolitis

OR

odds ratio

RXR

retinoid X receptor

ROP

retinopathy of prematurity

PVL

periventricular leukomalacia

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Hagberg, B., Hagberg, G., and Olow, I. (1993) The Changing Panorama of Cerebral Palsy in Sweden, Acta Pediatr. Scand. 82, 387–393.Google Scholar
  2. 2.
    Pharoah, P.O.D., Cooke, R.W.I., and Rosenbloom, L. (1990) Birthweight Specific Trends in Cerebral Palsy, Arch. Dis. Child. 65, 602–606.PubMedGoogle Scholar
  3. 3.
    Pharoah, P.O., Platt, M.J., and Cooke, T. (1996) The Changing Epidemiology of Cerebral Palsy, Arch. Dis. Child. 75, F169-F173.Google Scholar
  4. 4.
    Pharoah, P.O., Cooke, T., Johnson, M.A., King, R., and Mutch, L. (1998) Epidemiology of Cerebral Palsy in England and Scotland, 1984–9, Arch. Dis. Child. Fetal Neonatal Ed. 79, F21-F25.PubMedGoogle Scholar
  5. 5.
    Levine, M. (1990) Cerebral Ultrasound and Neurological Impairment: Telling the Future, Arch. Dis. Child. 65, 469–471.Google Scholar
  6. 6.
    Hagberg, B., Hagberg, G., Beckung, E., and Uvebrant, P. (2001) Changing Panorama of Cerebral Palsy in Sweden. VIII. Prevalence and Origin in the Birth Year Period 1991–94, Acta Paediatr. 90, 271–277.PubMedCrossRefGoogle Scholar
  7. 7.
    Piecuch, R.E., Leonard, C.H., Cooper, B.A., Kilpatrick, S.J., Schlueter, M.A., and Sola, A. (1997) Outcome of Infants Born at 24–26 Weeks' Gestation: II. Neurodeyelopmental Outcome, Obstet. Gynecol. 90, 809–814.CrossRefPubMedGoogle Scholar
  8. 8.
    Powls, A., Botting, N., Cooke, R.W., Stephenson, G., and Marlow, N. (1997) Visual Impairment in Very Low Birthweight Children, Arch. Dis. Child. Fetal Neonatal 76, F82-F87.Google Scholar
  9. 9.
    Cioni, G., Fazzi, B., Coluccini, M., Bartalena, L., Boldrini, A., and van Hof-van Duin, J. (1997) Cerebral Visual Impairment in Preterm Infants with Periventricular Leukomalacia, Pediatr. Neurol. 17, 331–338.CrossRefPubMedGoogle Scholar
  10. 10.
    Peterson, B.S., Vohr, B., Staib, L.H., Cannistraci, C.J., Dolberg, A., Schneider, K.C., Katz, K.H., Westerveld, M., Sparrow, S., Anderson, A.W., Duncan, C.C., Makuch, R.W., Gore, J.C., and Ment, L.R. (2000) Regional Brain Volume Abnormalities and Long-Term Cognitive Outcome in Preterm Infants, J. Am. Med. Assoc. 284, 1939–1947.CrossRefGoogle Scholar
  11. 11.
    Fulton, A.B., Hansen, R.M., Petersen, R.A., and Vanderveen, D.K. (2001) The Rod Photoreceptors in Retinopathy of Prematurity: An Electroretinographic Study, Arch. Ophthalmol. 119, 499–505.PubMedGoogle Scholar
  12. 12.
    Uauy, R., Peirano, P., Hoffman, D., Mena, P., Birch, D., and Birch, E. (1996) Role of Essential Fatty Acids in the Function of the Developing Nervous System, Lipids 31 (Suppl.), S167-S176.PubMedGoogle Scholar
  13. 13.
    Uany, R., Mena, P., and Rojas, C. (2000) Essential Fatty Acids in Early Life: Structural and Functional Role, Proc. Nutr. Soc. 59, 3–15.CrossRefGoogle Scholar
  14. 14.
    Uany, R., Peirano, P., Hoffman, D., Mena, P., Birch, D., and Birch, E. (1996) Role of Essential Fatty Acids in the Function of the Developing Nervous System, Lipids 31 (Suppl.), S167-S176.Google Scholar
  15. 15.
    Carlson, S.E., Montalto, M.B., Ponder, D.L., Werkman, S.H., and Korones, S.B. (1998) Lower Incidence of Necrotising Enterocolitis in Infants Fed a Preterm Formula with Egg Phospholipids, Pediatr. Res. 44, 491–498.PubMedGoogle Scholar
  16. 16.
    Tapia, J.L., Ramirez, R., Cifuentes, J., Fabres, J., Hübner, M.E., Bancalari, A., Mercado, E., Standen, J., and Escobar, M. (1998) The Effect of Early Dexamethasone Administration on Bronchopulmonary Dysplasia in Preterm Infants with Respiratory Distress Syndrome, J. Pediatr. 132, 48–52.CrossRefPubMedGoogle Scholar
  17. 17.
    Bunt, J.E., Carnielli, V.P., Darcos Wattimena, J.L., Hop, W.C., Sauer, P.J., and Zimmermann, L.J. (2000) The Effect in Premature Infants of Prenatal Corticosteroids on Endogenous Surfactant Synthesis as Measured with Stable Isotopes, Am. J. Respir. Crit. Care Med. 162, 844–849.PubMedGoogle Scholar
  18. 18.
    Greenough, A. (1998) Gains and Losses from Dexamethasone for Neonatal Chronic Lung Disease, Lancet 352, 835–836.CrossRefPubMedGoogle Scholar
  19. 19.
    Canterino, J.C., Verma, U., Visintainer, P.F., Elimian, A., Klein, S.A., and Tejani, N. (2001) Antenatal Steroids and Neonatal Periventricular Leukomalacia, Obstet. Gynecol. 97, 135–139.CrossRefPubMedGoogle Scholar
  20. 20.
    Ahlbom, E., Gogvadze, V., Chen, M., Celsi, G., and Ceccatelli, S. (2000) Prenatal Exposure to High Levels of Glucocorticoids Increases the Susceptibility of Cerebellar Granule Cells to Oxidative Stress-Induced Cell Death, Proc. Natl. Acad. Sci. USA 97, 14726–14730.CrossRefPubMedGoogle Scholar
  21. 21.
    Stark, A.R., Carlo, W.A., Tyson, J.E., Papile, L.A., Wright, L.L., Shankaran, S., Donovan, E.F., Oh, W., Bauer, C.R., Saha, S., Poole, W.K., and Stoll, B.J. (2001) Adverse Effects of Early Dexamethasone in Extremely-Low-Birth-Weight Infants. National Institute of Child Health and Human Development Neonatal Research Network, N. Engl. J. Med. 344, 95–101.CrossRefPubMedGoogle Scholar
  22. 22.
    Barrington, K.J. (2001) The Adverse Neuro-Developmental Effects of Postnatal Steroids in the Preterm Infant: A Systematic Review of RCTs, BMC Pediatr. 1, 1–14.CrossRefPubMedGoogle Scholar
  23. 23.
    Speer, C.P. (2001) New Insights into the Pathogenesis of Pulmonary Inflammation in Preterm Infants, Biol. Neonate 79, 205–209.CrossRefPubMedGoogle Scholar
  24. 24.
    Shinwell, E.S., Karplus, M., Reich, D., Weintraub, Z., Blazer, S., Bader, D., Yurman, S., Dolfin, T., Kogan, A., Dollberg, S., et al. (2000) Early Postnatal Dexamethasone Treatment and Increased Incidence of Cerebral Palsy, Arch. Dis. Child. Fetal Neonatal Ed. 83, F177-F181.CrossRefPubMedGoogle Scholar
  25. 25.
    Glozman, S., Green, P., and Yavin, E. (1998) Intraamniotic Ethyl Docosahexaenoate Administration Protects Fetal Rat Brain from Ischemic Stress, J. Neurochem. 70, 2484–2491.PubMedCrossRefGoogle Scholar
  26. 26.
    Crosby, A.J., Wahle, K.W., and Duthie, G.G. (1996) Modulation of Glutathione Peroxidase Activity in Human Vascular Endothelial Cells by Fatty Acids and the Cytokine Interleukin-1β, Biochim. Biophys. Acta 1303, 187–192.PubMedGoogle Scholar
  27. 27.
    Thies, F., Miles, E.A., Nebe-von-Caron, G., Powell, J.R., Hurst, T.L., Newsholme, E.A., and Calder, P.C. (2001) Influence of Dietary Supplementation with Long-Chain n−3 or n−6 Polyunsaturated Fatty Acids on Blood Inflammatory Cell Populations and Functions and on Plasma Soluble Adhesion Molecules in Healthy Adults, Lipids 36, 1183–1193.CrossRefPubMedGoogle Scholar
  28. 28.
    FAO/WHO (1978) Joint Consultation on The Role of Dietary Fats and Oils in Human Nutrition, FAO Nutrition Report no. 3, Food and Agriculture Organization, Rome.Google Scholar
  29. 29.
    Sinclair, A.J., and Crawford, M.A. (1972) The Accumulation of Arachidonate and Docosahexaenoate in the Developing Rat Brain, J. Neurochem. 19, 1753–1758.CrossRefPubMedGoogle Scholar
  30. 30.
    Sinclair, A.J., and Crawford, M.A. (1972) The Incorporation of Linolenic and Docosahexaenoic Acid into Liver and Brain Lipids of Developing Rats, FEBS Lett. 26 127–129.CrossRefPubMedGoogle Scholar
  31. 31.
    Sinclair, A.J. (1975) Long-Chain Polyunsaturated FA in the Mammalian Brain, Proc. Nutr. Soc. 34, 287–291.CrossRefPubMedGoogle Scholar
  32. 32.
    Leyton, J., Drury, P.J., and Crawford, M.A. (1987) Differential Oxidation of Saturated and Unsaturated Fatty Acids in vivo in the Rat, Br. J. Nutr. 57, 383–393.CrossRefPubMedGoogle Scholar
  33. 33.
    Cunnane, S.C., Menard, C.R., Likhodi, S.S., Brenna, J.T., and Crawford, M.A. (1999) Carbon Recycling into de novo Lipogenesis Is a Major Pathway in Neonatal Metabolism of Linoleate and α-Linolenate, Prostaglandins Leukot. Essent. Fatty Acids 60, 387–392.CrossRefPubMedGoogle Scholar
  34. 34.
    Pawlosky, R.J., Hibbeln, J.R., Novotny, J.A., and Salem, N., Jr. (2001) Physiological Compartmental Analysis of α-Linolenic Acid Metabolism in Adult Humans, J. Lipid Res. 42, 1257–1265.PubMedGoogle Scholar
  35. 35.
    Crawford, M.A. (2000) The Placental Delivery of Arachidonic and Docosahexaenoic Acids: Implications for the Lipid Nutrition of the Preterm Infant, Am. J. Clin. Nutr. 71, 275S-284S.PubMedGoogle Scholar
  36. 36.
    Leaf, A.A., Leighfield, M.J., Costeloe, K.L., and Crawford, M.A. (1992) Factors Affecting Long-Chain Polyunsaturated Fatty Acid Composition of Plasma Choline Phosphoglycerides in Preterm Infants, J. Pediatr. Gastroenterol. Nutr. 14, 300–308.PubMedGoogle Scholar
  37. 37.
    Carlson, S.E. (1996) Arachidonic Acid Status of Human Infants: Influence of Gestational Age at Birth and Diets with Very Long Chain n−3 and n−6 Fatty Acids, J. Nutr. 126, 1092S-1098S.PubMedGoogle Scholar
  38. 38.
    Crawford, M.A., Costeloe, K., Ghebremeske, K., and Phylactos, A. (1998) The Inadequacy of the Essential Fatty Acid Content of Present Preterm Feeds, Eur. J. Pediatr. 157 (Suppl.), S23-S27.PubMedGoogle Scholar
  39. 39.
    Leaf, A.A., Leighfield, M.J., Costeloe, K.L., and Crawford, M.A. (1992) Factors Affecting Long-Chain Polyunsaturated Fatty Acid Composition of Plasma Choline Phosphoglycerides in Preterm Infants, J. Pediatr. Gastroenterol. Nutr. 14, 300–308.PubMedGoogle Scholar
  40. 40.
    Nelson, K.B. (2002) The Epidemiology of Cerebral Palsy in Term Infants, Ment. Retard. Dev. Disabil. Res. Rev. 8, 146–150.CrossRefPubMedGoogle Scholar
  41. 41.
    von Minckwitz, G., Grischke, E.M., Schwab, S., Hettinger, S., Loibl, S., Aulmann, M., and Kaufmann, M. (2000) Predictive Value of Serum Interleukin-6 and −8 Levels in Preterm Labor or Rupture of the Membranes, Acta Obstet. Gynecol. Scand. 79, 667–672.CrossRefGoogle Scholar
  42. 42.
    Toti, P., and De Felice, C. (2001) Chorioamnionitis and Fetal/Neonatal Brain Injury, Biol. Neonate 79, 201–204.CrossRefPubMedGoogle Scholar
  43. 43.
    Duggan, P.J., Maalouf, E.F., Watts, T.L., Sullivan, M.H.F., Counsell, S.J., Allsop, J., Al-Nakib, L., Rutherford, M.A., Battin, M., Roberts, I., and Edwards, A.D. (2001) Intrauterine T-Cell Activation and Increased Proinflammatory Cytokine Concentrations in Preterm Infants with Cerebral Lesions, Lancet 358, 1699–1700.CrossRefPubMedGoogle Scholar
  44. 44.
    Nelson, K.B., Dambrosia, J.M., Grether, J.K., and Phillips, T.M. (1998) Neonatal Cytokines and Coagulation Factors in Children with Cerebral Palsy, Ann. Neurol. 44, 665–675.CrossRefPubMedGoogle Scholar
  45. 45.
    Harbige, L.S., Yeatman, N., Amor, S., and Crawford, M.A. (1995) Prevention of Experimental Auto-Immune Encephalomyelitis in Lewis Rats by a Novel Fungal Source of γ-Linolenic Acid, Br. J. Nutr. 74, 701–715.CrossRefPubMedGoogle Scholar
  46. 46.
    Crawford, M.A., Costeloe, K., Doyle, W., Leighfield, M.J., Lennon, E.A., and Meadows, N. (1990) Potential Diagnostic Value of the Umbilical Artery as a Definition of Neural Fatty Acid Status of the Fetus During Its Growth, Biochem. Soc. Trans. 18, 761–766.PubMedGoogle Scholar
  47. 47.
    Leaf, A.A., Leighfield, M.J., Costeloe, K.L., and Crawford, M.A. (1992) Factors Affecting Long-Chain Polyunsaturated Fatty Acid Composition of Plasma Choline Phosphoglycerides in Preterm Infants, J. Pediatr. Gastroenterol. Nutr. 14, 300–308.PubMedCrossRefGoogle Scholar
  48. 48.
    Leaf, A.A., Leighfield, M.J., Costeloe, K.L., and Crawford, M.A. (1992) Long-Chain Polyunsaturated Fatty Acids in Fetal Growth, Early Hum. Dev. 30, 183–191.CrossRefPubMedGoogle Scholar
  49. 49.
    Rump, P., Mensink, R.P., Kester, A.D., and Hornstra, G. (2001) Essential Fatty Acid Composition of Plasma Phospholipids and Birth Weight: A Study in Term Neonates, Am. J. Clin. Nutr. 73, 797–806.PubMedGoogle Scholar
  50. 50.
    Daneshmand, S.S., Chmait, R.H., Moore, T.R., and Bogic, L. (2002) Preterm Premature Rupture of Membranes: Vascular Endothelial Growth Factor and Its Association with Histologic Chorioamnionitis, Am. J. Obstet. Gynecol. 187, 1131–1136.CrossRefPubMedGoogle Scholar
  51. 51.
    Levin, A.A., Sturzenbecker, L.J., Kazmer, S., Bosakowski, T., Huselton, C., Allenby, G., Speck, J., Kratzeisen, C., Rosenberger, M., Lovey, A., et al. (1992) 9-cis Retinoic Acid Stereo-isomer Binds and Activates the Nuclear Receptor RXR-α, Nature 355, 359–361.CrossRefPubMedGoogle Scholar
  52. 52.
    Chawla, A., Repa, J.J., Evans, R.M., and Mangelsdorf, D.J. (2001) Opening the X-Files, Science 294, 1866–1870.CrossRefPubMedGoogle Scholar
  53. 53.
    de Urquiza, A.M., Liu, S., Sjoberg, M., Zetterstrom, R.H., Griffiths, W., Sjovall, J., and Perlmann, T. (2000) Docosahexaenoic Acid, a Ligand for the Retinoid X Receptor in Mouse Brain, Science 290, 2140–2144.CrossRefPubMedGoogle Scholar
  54. 54.
    Hibbeln, J.R. (1998) Fish Consumption and Major Depression, Lancet 351, 1213–1215. Comment in: Lancet 352, 71–72.CrossRefPubMedGoogle Scholar
  55. 55.
    Ikemoto, A., Nitta, A., Furukawa, S., Ohishi, M., Nakamura, A., Fujii, Y., and Okuyama, H. (2000) Dietary n−3 Fatty Acid Deficiency Decreases Nerve Growth Factor Content in Rat Hippocampus, Neurosci. Lett. 285, 99–102.CrossRefPubMedGoogle Scholar
  56. 56.
    Kitajka, K., Puskas, L.G., Zvara, A., Hackler, L., Jr., Barcelo-Coblijn, G., Yeo, Y.K., and Farkas, T. (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.CrossRefPubMedGoogle Scholar
  57. 57.
    FAO/WHO (1994) Joint Consultation on The Role of Dietary Fats and Oils in Human Nutrition, Food and Agriculture Organization, Rome.Google Scholar
  58. 58.
    Hibbeln, J.R. (2001) Seafood Consumption and Homicide Mortality. A Cross-National Ecological Analysis, World Rev. Nutr. Diet. 88, 41–46.PubMedCrossRefGoogle Scholar
  59. 59.
    Hibbeln, J.R., (2002) Seafood Consumption, the DHA Content of Mothers' Milk and Prevalence Rates of Postpartum Depression: A Cross-National, Ecological Analysis, J. Affect. Disord. 69, 15–29.CrossRefPubMedGoogle Scholar
  60. 60.
    SanGiovanni, J.P., Berkey, C.S., Dwyer, J.T., and Colditz, G.A. (2000) Dietary Essential Fatty Acids, Long-Chain Polyunsaturated Fatty Acids, and Visual Resolution Acuity in Healthy Full Term Infants: A Systematic Review, Early Hum. Dev. 57, 165–188.CrossRefPubMedGoogle Scholar
  61. 61.
    Birch, E.E., Garfield, S., Hoffman, D.E., Uauy, R., and Birch, D.G. (2000) A Randomised Trial of Early Dietary Supply of Long-Chain Polyunsaturated Fatty Acids and Mental Development in Term Infants, Dev. Med. Child. Neurol. 42, 174–181.CrossRefPubMedGoogle Scholar
  62. 62.
    Saugstad, O.D. (1996) Mechanisms of Tissue Injury by Oxygen Radicals: Implications for Neonatal Disease, Acta Paediatr. 85, 1–4.PubMedGoogle Scholar
  63. 63.
    Phylactos, A.C., Leaf, A.A., Costeloe, K., and Crawford, M.A. (1995) Erythrocyte Cupric/Zinc Superoxide Dismutase Exhibits Reduced Activity in Preterm and Low Birthweight Infants at Birth, Acta Paediatr. 84, 1421–1425.PubMedGoogle Scholar
  64. 64.
    Raju, T.N., Langenberg, P., Bhutani, V., and Quinn, G.E. (1997) Vitamin E Prophylaxis to Reduce Retinopathy of Prematurity: A Reappraisal of Published Trials, J. Pediatr. 131, 844–850.CrossRefPubMedGoogle Scholar
  65. 65.
    Budowski, P., Leighfield, M.J., and Crawford, M.A. (1987) Nutritional Encephalomalacia in the Chick: An Exposure of the Vulnerable Period for Cerebellar Development and the Possible Need for Both ω6 and ω3 Fatty Acids, Br. J. Nutr. 58, 511–520.CrossRefPubMedGoogle Scholar
  66. 66.
    Budowski, P. (1996) The Omega-3 Fatty Acid Peroxidation Paradox, Redox Rep. 2, 75–77.Google Scholar
  67. 67.
    Budowski, P., Hawkey, C.M., and Crawford, M.A. (1980) L'Effet Protecteur de l'Acide α-Linolenique sur l'Encephalomalacie chez le Poulet, Ann. Nutr. Alim. 34, 389–400.Google Scholar
  68. 68.
    Crawford, M.A., Costeloe, K., Ghebremeskel, K., Phylactos, A., Skirvin, L., and Stacey, F. (1997) Are Deficits of Arachidonic and Docosahexaenoic Acids Responsible for the Neural and Vascular Complications of Preterm Babies? Am. J. Clin. Nutr. 66, 1032S-1041S.PubMedGoogle Scholar
  69. 69.
    Ghosh, P., Butsanis, D., Ghebremeskel, K., Crawford, M.A., and Poston, L. (2001) Abnormal Fatty Acid Composition and Small Artery Function in Offspring of Rats Fed a High Fat Diet in Pregnancy, J. Physiol. 533, 815–822.CrossRefPubMedGoogle Scholar
  70. 70.
    Topp, M., Langhoff-Roos, J., Uldall, P., and Kristensen, J. (1996) Intrauterine Growth and Gestational Age in Preterm Infants with Cerebral Palsy, Early Hum. Dev. 44, 27–36.CrossRefPubMedGoogle Scholar
  71. 71.
    Hirafuji, M., Machida, T., Tsunoda, M., Miyamoto, A., and Minami, M. (2002) Docosahexaenoic Acid Potentiates Interleukin-1β Induction of Nitric Oxide Synthase Through Mechanism Involving p44/42 MAPK Activation in Rat Vascular Smooth Muscle Cells, Br. J. Pharmacol. 136, 613–619.CrossRefPubMedGoogle Scholar
  72. 72.
    Glozman, S., Green, P., and Yavin, E. (1998) Intraamniotic Ethyl Docosahexaenoate Administration Protects Fetal Rat Brain from Ischemic Stress, Neurochemistry 70, 2484–2491.Google Scholar
  73. 73.
    Beckman, J.S. (1991) The Double-Edged Role of Nitric Oxide in Brain Function and Superoxide-Mediated Injury, J. Dev. Physiol. 15, 53–59.PubMedGoogle Scholar
  74. 74.
    Bolanos, J.P., and Almeida, A. (1999) Roles of Nitric Oxide in Brain Hypoxia-Ischemia, Biochim. Biophys. Acta 1411, 415–436.CrossRefPubMedGoogle Scholar
  75. 75.
    Homayoun, P., Rodriguez de Turco, E.B., Parkins, N.E., Lane, D.C., Soblosky, J., Carey, M.E., and Bazan, N.G. (1997) Delayed Phospholipid Degradation in Rat Brain After Traumatic Brain Injury, J. Neurochem. 69, 199–205.PubMedCrossRefGoogle Scholar
  76. 76.
    Yoon, B.H., Romero, R., Kim, C.J., Jun, J.K., Gomez, R., Choi, J.H., and Syn, H.C. (1995) Amniotic Fluid Interleukin-6, a Sensitive Test for Antenatal Diagnosis of Acute Inflammatory Lesions of Preterm Placenta and Prediction of Perinatal Morbidity, Am. J. Obstet. Gynecol. 172, 960–970.CrossRefPubMedGoogle Scholar
  77. 77.
    Beckman, J.S., and Koppenol W.H. (1996) Nitric Oxide, Superoxide, and Peroxynitrite, the Good, the Bad, and Ugly, Am. J. Physiol. 271, C1424-C1437.PubMedGoogle Scholar
  78. 78.
    Thies, F., Garry, J.M., Yaqoob, P., Rerkasem, K., Williams, J., Shearman, C.P., Gallagher, P.J., Calder, P.C., and Grimble, R.F. (2003) Association of n−3 Polyunsaturated Fatty Acids with Stability of Atherosclerotic Plaques: A Randomised Controlled Trial, Lancet 361, 477–485.CrossRefPubMedGoogle Scholar
  79. 79.
    Engler, M.M., Engler, M.B., Pierson, D.M., Molteni, L.B., and Molteni, A. (2003) Effects of Docosahexaenoic Acid on Vascular Pathology and Reactivity in Hypertension, Exp. Biol. Med. 228, 299–307.Google Scholar
  80. 80.
    Crawford, M.A., Costeloe, K., Ghebremeskel, K., and Phylactos, A. (1998) The Inadequacy of the Essential Fatty Acid Content of Present Preterm Feeds, Eur. J. Pediatr. 157 (Suppl. 1), S23-S27.PubMedGoogle Scholar
  81. 81.
    Hindenes, J.O., Nerdal, W., Guo, W., Di, L., Small, D.M., and Holmsen, H. (2000) Physical Properties of the Transmembrane Signal Molecule, sn-1-Stearoyl-2-arachidonoylglycerol. Acyl Chain Segregation and Its Biochemical Implications, J. Biol. Chem. 275, 6857–6867.CrossRefPubMedGoogle Scholar
  82. 82.
    Crawford, M.A. (2000) The Placental Delivery of Arachidonic and Docosahexaenoic Acids: Implications for the Lipid Nutrition of the Preterm Infant, Am. J. Clin. Nutr. 71, 275S-284S.PubMedGoogle Scholar
  83. 83.
    Williams, G., and Crawford, M.A. (1987) Comparison of the Fatty Acid Component in Structural Lipids from Dolphins, Zebra and Giraffe: Possible Evolutionary Implications, J. Zool. Lond. 213, 673–684.CrossRefGoogle Scholar
  84. 84.
    Crawford, M.A., Casperd, N.M., and Sinclair, A.J. (1976) The Long-Chain Metabolites of Linoleic and Linolenic Acids in Liver and Brain in Herbivores and Carnivores, Comp. Biochem. Physiol. 54B, 395–401.Google Scholar
  85. 85.
    Crawford, M.A., Bloom, M., Broadhurst, C.L., Schmidt, W.F., Cunnane, S.C., Galli, C., Ghebremeskel, K., Linseisen, F., Lloyd-Smith, J., and Parkington, J. (1999) Evidence for the Unique Function of DHA During the Evolution of the Modern Hominid Brain, Lipids 34, S39-S47.CrossRefPubMedGoogle Scholar
  86. 86.
    Taylor, P.D., Khan, I.Y., Lakasing, L., Dekou, V., O'Brien-Coker, I., Mallet, A.I., Hanson, M.A., and Poston, L. (2003) Uterine Artery Function in Pregnant Rats Fed a Diet Supplemented with Animal Lard, Exp. Physiol. 88, 389–398.CrossRefPubMedGoogle Scholar
  87. 87.
    Golfetto, I. (2003) Essentiality of Polyunsaturated Fatty Acids in Early Development, Ph.D. Thesis, London Metropolitan University, London.Google Scholar

Copyright information

© AOCS Press 2003

Authors and Affiliations

  • M. A. Crawford
    • 4
  • I. Golfetto
    • 4
  • K. Ghebremeskel
    • 4
  • Y. Min
    • 4
  • T. Moodley
    • 4
  • L. Poston
    • 1
  • A. Phylactos
    • 4
  • S. Cunnane
    • 2
  • W. Schmidt
    • 3
  1. 1.Fetal Research Unit, United Medical and Dental Schools of Guy's and St Thomas's HospitalsUniversity of LondonLondonUK
  2. 2.Department of Nutritional SciencesUniversity of TorontoTorontoCanada
  3. 3.USDA, ARSBeltsville
  4. 4.Institute of Brain Chemistry and Human NutritionThe London Metropolitan UniversityLondonUK

Personalised recommendations