Altered Lipid Metabolism in Brain Injury and Disorders

  • Rao Muralikrishna Adibhatla
  • J. F. Hatcher
Part of the Subcellular Biochemistry book series (SCBI, volume 49)


Deregulated lipid metabolism may be of particular importance for CNS injuries and disorders, as this organ has the highest lipid concentration next to adipose tissue. Atherosclerosis (a risk factor for ischemic stroke) results from accumulation of LDL-derived lipids in the arterial wall. Pro-inflammatory cytokines (TNF-α and IL-1), secretory phospholipase A2 IIA and lipoprotein-PLA2 are implicated in vascular inflammation. These inflammatory responses promote atherosclerotic plaques, formation and release of the blood clot that can induce ischemic stroke. TNF-α and IL-1 alter lipid metabolism and stimulate production of eicosanoids, ceramide, and reactive oxygen species that potentiate CNS injuries and certain neurological disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Low levels of neurosteroids were related to poor outcome in many brain pathologies. Apolipoprotein E is the principal cholesterol carrier protein in the brain, and the gene encoding the variant Apolipoprotein E4 is a significant risk factor for Alzheimer’s disease. Parkinson’s disease is to some degree caused by lipid peroxidation due to phospholipases activation. Niemann-Pick diseases A and B are due to acidic sphingomyelinase deficiency, resulting in sphingomyelin accumulation, while Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes, resulting in defective cholesterol transport and cholesterol accumulation. Multiple sclerosis is an autoimmune inflammatory demyelinating condition of the CNS. Inhibiting phospholipase A2 attenuated the onset and progression of experimental autoimmune encephalomyelitis. The endocannabinoid system is hypoactive in Huntington’s disease. Ethyl-eicosapetaenoate showed promise in clinical trials. Amyotrophic lateral sclerosis causes loss of motorneurons. Cyclooxygenase-2 inhibition reduced spinal neurodegeneration in amyotrophic lateral sclerosis transgenic mice. Eicosapentaenoic acid supplementation provided improvement in schizophrenia patients, while the combination of (eicosapentaenoic acid + docosahexaenoic acid) provided benefit in bipolar disorders. The ketogenic diet where >90% of calories are derived from fat is an effective treatment for epilepsy. Understanding cytokine-induced changes in lipid metabolism will promote novel concepts and steer towards bench-to-bedside transition for therapies.


Atherosclerosis Cholesterol Inflammation Neurodegenerative diseases Stroke 


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  1. Aagaard, L. and Rossi, J. J. RNAi therapeutics: Principles, prospects and challenges. Adv Drug Deliv Rev 59 (2007) 75–86.PubMedCrossRefGoogle Scholar
  2. Adibhatla, R. M. and Hatcher, J. F. Cytidine 5'-diphosphocholine (CDP-choline) in stroke and other CNS disorders. Neurochem Res 30 (2005) 15–23.PubMedCrossRefGoogle Scholar
  3. Adibhatla, R. M. and Hatcher, J. F. Phospholipase A2, reactive oxygen species, and lipid peroxidation in cerebral ischemia. Free Radic Biol Med 40 (2006) 376–387.CrossRefGoogle Scholar
  4. Adibhatla, R. M. and Hatcher, J. F. Role of lipids in brain injury and diseases. Future Lipidol 2 (2007) 403–422.PubMedCrossRefGoogle Scholar
  5. Adibhatla, R. M. and Hatcher, J. F. Integration of cytokine biology and lipid metabolism in stroke. Front Biosci 13 (2008) 1250–1270.PubMedCrossRefGoogle Scholar
  6. Adibhatla, R. M., Hatcher, J. F. and Dempsey, R. J. Lipids and lipidomics in brain injury and diseases. AAPS J 8 (2006a) E314–E321.CrossRefGoogle Scholar
  7. Adibhatla, R. M., Hatcher, J. F., Larsen, E. C., Chen, X., Sun, D. and Tsao, F. CDP-choline significantly restores the phosphatidylcholine levels by differentially affecting phospholipase A2 and CTP-phosphocholine cytidylyltransferase after stroke. J Biol Chem 281 (2006b) 6718–6725.CrossRefGoogle Scholar
  8. Agar, J. and Durham, H. Relevance of oxidative injury in the pathogenesis of motor neuron diseases. Amyotroph Lateral Scler Other Motor Neuron Disord 4 (2003) 232–242.PubMedCrossRefGoogle Scholar
  9. Ariza, M., Pueyo, R., Matarin, M. del M., Junque, C., Mataro, M., Clemente, I., Moral, P., Poca, M. A., Garnacho, A. and Sahuquillo, J. Influence of APOE polymorphism on cognitive and behavioural outcome in moderate and severe traumatic brain injury. J Neurol Neurosurg Psychiatry 77 (2006) 1191–1193.PubMedCrossRefGoogle Scholar
  10. Berger, G. E., Smesny, S. and Amminger, G. P. Bioactive lipids in schizophrenia. Int Rev Psychiatry 18 (2006) 85–98.PubMedCrossRefGoogle Scholar
  11. Bialer, M., Johannessen, S. I., Kupferberg, H. J., Levy, R. H., Perucca, E. and Tomson, T. Progress report on new antiepileptic drugs: A summary of the Eigth Eilat Conference (EILAT VIII). Epilepsy Res 73 (2007) 1–52.PubMedCrossRefGoogle Scholar
  12. Bonifacio, M. J., Palma, P. N., Almeida, L. and Soares-da-Silva, P. S. Catechol-O-methyltransferase and its inhibitors in Parkinson’s disease. CNS Drug Rev 13 (2007) 352–379.PubMedCrossRefGoogle Scholar
  13. Bough, K. J. and Rho, J. M. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia 48 (2007) 43–58.PubMedCrossRefGoogle Scholar
  14. Boullier, A., Friedman, P., Harkewicz, R., Hartvigsen, K., Green, S. R., Almazan, F., Dennis, E. A., Steinberg, D., Witztum, J. L. and Quehenberger, O. Phosphocholine as a pattern recognition ligand for CD36. J Lipid Res 46 (2005) 969–976.PubMedCrossRefGoogle Scholar
  15. Bratton, D. L. and Henson, P. M. Autoimmunity and apoptosis: Refusing to go quietly. Nat Med 11 (2005) 26–27.PubMedCrossRefGoogle Scholar
  16. Burns, M. P. and Duff, K. Brain on steroids resists neurodegeneration. Nat Med 10 (2004) 675–676.PubMedCrossRefGoogle Scholar
  17. Caballero, J. and Nahata, M. Do statins slow down Alzheimer's disease? A review. J Clin Pharm Ther 29 (2004) 209–213.PubMedCrossRefGoogle Scholar
  18. Carlson, N. G. and Rose, J. W. Antioxidants in multiple sclerosis: Do they have a role in therapy? CNS Drugs 20 (2006) 433–441.PubMedCrossRefGoogle Scholar
  19. Chang, M.-K., Binder, C. J., Miller, Y. I., Subbanagounder, G., Silverman, G. J., Berliner, J. A. and Witztum, J. L. Apoptotic cells with oxidation-specific epitopes are immunogenic and proinflammatory. J Exp Med 200 (2004) 1359–1370.PubMedCrossRefGoogle Scholar
  20. Clifford, J. J., Drago, J., Natoli, A. L., Wong, J. Y. F., Kinsella, A., Waddington, J. L. and Vaddadi, K. S. Essential fatty acids given from conception prevent topographies of motor deficit in a transgenic model of Huntington's disease. Neuroscience 109 (2002) 81–88.PubMedCrossRefGoogle Scholar
  21. Crack, P. J. and Taylor, J. M. Reactive oxygen species and the modulation of stroke. Free Radic Biol Med 38 (2005) 1433–1444.PubMedCrossRefGoogle Scholar
  22. Cunningham, T. J., Yao, L., Oetinger, M., Cort, L., Blankenhorn, E. P. and Greensteinm, J. I. Secreted phospholipase A2 activity in experimental autoimmune encephalomyelitis and multiple sclerosis. J Neuroinflammation (2006) 3 doi: 10.1186/742-2094-3-26.Google Scholar
  23. Degroot, A. and Nomikos, G. G. In vivo neurochemical effects induced by changes in endocannabinoid neurotransmission. Curr Opin Pharmacol 7 (2007) 62–68.PubMedCrossRefGoogle Scholar
  24. Djebaili, M., Guo, Q., Pettus, E. H., Hoffman, S. W. and Stein, D. G. The neurosteroids progesterone and allopregnanolone reduce cell death, gliosis, and functional deficits after traumatic brain injury in rats. J Neurotrauma 22 (2005) 106–118.PubMedCrossRefGoogle Scholar
  25. Dringen, R. Metabolism and functions of glutathione in brain. Prog Neurobiol 62 (2000) 649–671.PubMedCrossRefGoogle Scholar
  26. Ehehalt, R., Keller, P., Haass, C., Thiele, C. and Simons, K. Amyloidogenic processing of the Alzheimer β-amyloid precursor protein depends on lipid rafts. J Cell Biol 160 (2003) 113–123.PubMedCrossRefGoogle Scholar
  27. Elkind, M. S. Inflammation, atherosclerosis, and stroke. Neurologist 12 (2006) 140–148.PubMedCrossRefGoogle Scholar
  28. Emsley, H. C. A. and Tyrrell, P. J. Inflammation and infection in clinical stroke. J Cereb Blood Flow Metab 22 (2002) 1399–1419.PubMedCrossRefGoogle Scholar
  29. Farooqui, A. A., Ong, W.-Y. and Horrocks, L. A. Inhibitors of brain phospholipase A2 activity: Their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol Rev 58 (2006) 591–620.PubMedCrossRefGoogle Scholar
  30. Feng, L. and Prestwich, G. D. (2006) Functional Lipidomics. p. 329, CRC Press, Taylor & Francis Group, Boca RatonGoogle Scholar
  31. Futerman, A. H. and van Meer, G. The cell biology of lysosomal storage disorders. Nat Rev Mol Cell Biol 5 (2004) 554–565.PubMedCrossRefGoogle Scholar
  32. Gao, S., Zhang, R. L., Greenberg, M. E., Sun, M., Chen, X., Levison, B. S., Salomon, R. G. and Hazen, S. L. Phospholipid hydroxyalkenals, a subset of recently discovered endogenous CD36 ligands, spontaneously generate novel furan-containing phospholipids lacking CD36 binding activity in vivo. J Biol Chem 281 (2006) 31298–31308.PubMedCrossRefGoogle Scholar
  33. Garcia-Calvo, M., Lisnock, J., Bull, H. G., Hawes, B. E., Burnett, D. A., Braun, M. P., Crona, J. H., Davis, H. R., Jr., Dean, D. C., Detmers, P. A., Graziano, M. P., Hughes, M., MacIntyre, D. E., Ogawa, A., O'Neill, K. A., Iyer, S. P. N., Shevell, D. E., Smith, M. M., Tang, Y. S., Makarewicz, A. M., Ujjainwalla, F., Altmann, S. W., Chapman, K. T. and Thornberry, N. A. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci USA 102 (2005) 8132–8137.PubMedCrossRefGoogle Scholar
  34. Gasior, M., Rogawski, M. A. and Hartman, A. L. Neuroprotective and disease-modifying effects of the ketogenic diet. Behav Pharmacol 17 (2006) 431–439.PubMedCrossRefGoogle Scholar
  35. Ghesquiere, S. A. I., Gijbels, M. J. J., Anthonsen, M. W., van Gorp, P. J. J., van der Made, I., Johansen, B., Hofker, M. H. and de Winther, M. P. J. Macrophage-specific overexpression of group IIa sPLA2 increases atherosclerosis and enhances collagen deposition. J Lipid Res 46 (2005) 201–210.Google Scholar
  36. Griffin, L. D., Gong, W., Verot, L. and Mellon, S. H. Niemann-Pick type C disease involves disrupted neurosteroidogenesis and responds to allopregnanolone. Nature Med 10 (2004) 704–711.PubMedCrossRefGoogle Scholar
  37. Grimm, M. O. W., Grimm, H. S., Patzold, A. J., Zinser, E. G., Halonen, R., Duering, M., Tschape, J.-A., Strooper, B. D., Muller, U., Shen, J. and Hartmann, T. Regulation of cholesterol and sphingomyelin metabolism by amyloid-β and presenilin. Nat Cell Biol 7 (2005) 1118–1123.PubMedCrossRefGoogle Scholar
  38. Hall, E. D. and Springer, J. E. Neuroprotection and acute spinal cord injury: A reappraisal. NeuroRx 1 (2004) 80–100.PubMedCrossRefGoogle Scholar
  39. Hansson, G. K. and Libby, P. The immune response in atherosclerosis: A double-edged sword. Nat Rev Immunol 6 (2006) 508–519.PubMedCrossRefGoogle Scholar
  40. Hartmann, T., Kuchenbecker, J. and Grimm, M. O. W. Alzheimer's disease: The lipid connection. J Neurochem 103 (2007) 159–170.PubMedCrossRefGoogle Scholar
  41. Hauser, R. A. and Zesiewicz, T. A. Advances in the pharmacologic management of early Parkinson disease. Neurologist 13 (2007) 126–132.PubMedCrossRefGoogle Scholar
  42. Herrup, K., Neve, R., Ackerman, S. L. and Copani, A. Divide and die: Cell cycle events as triggers of nerve cell death. J Neurosci 24 (2004) 9232–9239.PubMedCrossRefGoogle Scholar
  43. Horrobin, D. (2002). The lipid hypothesis of schizophrenia. In E. R. Skinner (eds.), Brain Lipids and Disorders in Biological Psychiatry, pp. 39–52. Amsterdam: Elsevier Science.CrossRefGoogle Scholar
  44. Jellinger, K. A. Head injury and dementia. Curr Opin Neurol 17 (2004) 719–723.PubMedCrossRefGoogle Scholar
  45. Kadl, A., Bochkov, V. N., Huber, J. and Leitinger, N. Apoptotic cells as sources for biologically active oxidized phospholipids. Antioxid Redox Signal 6 (2004) 311–320.PubMedCrossRefGoogle Scholar
  46. Karishma, K. K. and Herbert, J. Dehydroepiandrosterone (DHEA) stimulates neurogenesis in the hippocampus of the rat, promotes survival of newly formed neurons and prevents corticosterone-induced suppression. Eur J Neurosci 16 (2002) 445–453.PubMedCrossRefGoogle Scholar
  47. Kinnunen, P. K. J. and Holopainen, J. M. Sphingomyelinase activity of LDL – A link between atherosclerosis, ceramide, and apoptosis? Trends Cardiovasc Med 12 (2002) 37–42.PubMedCrossRefGoogle Scholar
  48. Kougias, P., Chai, H., Lin, P. H., Lumsden, A. B., Yao, Q. and Chen, C. Lysophosphatidylcholine and secretory phospholipase A2 in vascular disease: Mediators of endothelial dysfunction and atherosclerosis. Med Sci Monit 12 (2006) RA5–R16.PubMedGoogle Scholar
  49. Kronke, M. and Adam-Klages, S. Role of caspases in TNF-mediated regulation of cPLA2. FEBS Lett 531 (2002) 18–22.PubMedCrossRefGoogle Scholar
  50. Kunst, C. B. Complex genetics of amyotrophic lateral sclerosis. Am J Hum Genet 75 (2004) 933–947.PubMedCrossRefGoogle Scholar
  51. Kunz, A., Anrather, J., Zhou, P., Orio, M. and Iadecola, C. Cyclooxygenase-2 does not contribute to postischemic production of reactive oxygen species. J Cereb Blood Flow Metab 27 (2007) 545–551.PubMedCrossRefGoogle Scholar
  52. Lapchak, P. A., Chapman, D. F., Nunez, S. Y. and Zivin, J. A. Dehydroepiandrosterone sulfate is neuroprotective in a reversible spinal cord ischemia model: Possible involvement of GABAA receptors. Stroke 31 (2000) 1953–1956.PubMedGoogle Scholar
  53. LaRoche, S. M. A new look at the second-generation antiepileptic drugs: A decade of experience. Neurologist 13 (2007) 133–139.PubMedCrossRefGoogle Scholar
  54. Larsen, E. C., Hatcher, J. F. and Adibhatla, R. M. Effect of tricyclodecan-9-yl potassium xanthate (D609) on phospholipid metabolism and cell death during oxygen-glucose deprivation in PC12 cells. Neuroscience 146 (2007) 946–961.PubMedCrossRefGoogle Scholar
  55. Lavi, S., McConnell, J. P., Rihal, C. S., Prasad, A., Mathew, V., Lerman, L. O. and Lerman, A. Local production of lipoprotein-associated phospholipase A2 and lyso-phosphatidylcholine in the coronary circulation: Association with early coronary atherosclerosis and endothelial dysfunction in humans. Circulation 115 (2007) 2715–2721.PubMedCrossRefGoogle Scholar
  56. Liu, K. J. and Rosenberg, G. A. Matrix metalloproteinases and free radicals in cerebral ischemia. Free Radic Biol Med 39 (2005) 71–80.CrossRefGoogle Scholar
  57. Liu, X., Lovell, M. A. and Lynn, B. C. Development of a method for quantification of acrolein-deoxyguanosine adducts in DNA using isotope dilution-capillary LC/MS/MS and its application to human brain tissue. Anal Chem 77 (2005) 5982–5989.PubMedCrossRefGoogle Scholar
  58. Lukiw, W. J., Cui, J.-G., Marcheselli, V. L., Bodker, M., Botkjaer, A., Gotlinger, K., Serhan, C. N. and Bazan, N. G. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest 115 (2005) 2774–2783.PubMedCrossRefGoogle Scholar
  59. Lynch, J. R., Wang, H., Mace, B., Leinenweber, S., Warner, D. S., Bennett, E. R., Vitek, M. P., McKenna, S. and Laskowitz, D. T. A novel therapeutic derived from apolipoprotein E reduces brain inflammation and improves outcome after closed head injury. Exp Neurol 192 (2005) 109–116.PubMedCrossRefGoogle Scholar
  60. Maccarrone, M., Battista, N. and Centonze, D. The endocannabinoid pathway in Huntington's disease: A comparison with other neurodegenerative diseases. Prog Neurobiol 81 (2007) 349–379.PubMedCrossRefGoogle Scholar
  61. Mahmood, A., Lu, D., Qu, C., Goussev, A. and Chopp, M. Treatment of traumatic brain injury with a combination therapy of marrow stromal cells and atorvastatin in rats. Neurosurgery 60 (2007) 546–554.PubMedCrossRefGoogle Scholar
  62. Mandavilli, A. The amyloid code. Nat Med 12 (2006) 747–751.PubMedCrossRefGoogle Scholar
  63. Margaill, I., Plotkine, M. and Lerouet, D. Antioxidant strategies in the treatment of stroke. Free Radic Biol Med 39 (2005) 429–443.PubMedCrossRefGoogle Scholar
  64. Mariani, E., Polidori, M. C., Cherubini, A. and Mecocci, P. Oxidative stress in brain aging, neurodegenerative and vascular diseases: An overview. J Chromatog B 827 (2005) 65–75.CrossRefGoogle Scholar
  65. Marusic, S., Leach, M. W., Pelker, J. W., Azoitei, M. L., Uozumi, N., Cui, J., Shen, M. W. H., DeClercq, C. M., Miyashiro, J. S., Carito, B. A., Thakker, P., Simmons, D. L., Leonard, J. P., Shimizu, T. and Clark, J. D. Cytosolic phospholipase A2α-deficient mice are resistant to experimental autoimmune encephalomyelitis. J Exp Med 202 (2005) 841–851.PubMedCrossRefGoogle Scholar
  66. Marx, C. E., Stevens, R. D., Shampine, L. J., Uzunova, V., Trost, W. T., Butterfield, M. I., Massing, M. W., Hamer, R. M., Morrow, A. L. and Lieberman, J. A. Neuroactive steroids are altered in schizophrenia and bipolar disorder: Relevance to pathophysiology and therapeutics. Neuropsychopharmacology 31 (2006a) 1249–1263.Google Scholar
  67. Marx, C. E., Trost, W. T., Shampine, L. J., Stevens, R. D., Hulette, C. M., Steffens, D. C., Ervin, J. F., Butterfield, M. I., Blazer, D. G., Massing, M. W. and Lieberman, J. A. The neurosteroid allopregnanolone is reduced in prefrontal cortex in Alzheimer's disease. Biol Psych 60 (2006b) 1287–1294.CrossRefGoogle Scholar
  68. Mattson, M. P., Cutler, R. G. and Jo, D. G. Alzheimer peptides perturb lipid-regulating enzymes. Nat Cell Biol 7 (2005) 1045–1047.PubMedGoogle Scholar
  69. Maxfield, F. R. and Tabas, I. Role of cholesterol and lipid organization in disease. Nature 438 (2005) 612–621.PubMedCrossRefGoogle Scholar
  70. McColl, B. W., Rothwell, N. J. and Allan, S. M. Systemic inflammatory stimulus potentiates the acute phase and CXC chemokine responses to experimental stroke and exacerbates brain damage via interleukin-1- and neutrophil-dependent mechanisms. J Neurosci 27 (2007) 4403–4412.PubMedCrossRefGoogle Scholar
  71. Mehta, S. L., Manhas, N. and Raghubir, R. Molecular targets in cerebral ischemia for developing novel therapeutics. Brain Res Rev 54 (2007) 34–66.PubMedCrossRefGoogle Scholar
  72. Minghetti, L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropath Exp Neurol 63 (2004) 901–910.PubMedGoogle Scholar
  73. Moses, G. S., Jensen, M. D., Lue, L. F., Walker, D. G., Sun, A. Y., Simonyi, A. and Sun, G. Y. Secretory PLA2-IIA: A new inflammatory factor for Alzheimer's disease. J Neuroinflammation 3 (2006) doi:10.1186/742-2094-3-28.Google Scholar
  74. Muma, N. A. Transglutaminase is linked to neurodegenerative diseases. J Neuropathol Exp Neurol 66 (2007) 258–263.PubMedCrossRefGoogle Scholar
  75. Nicolo, D., Varadhachary, A. S. and Monestier, M. Atherosclerosis, antiphospholipid syndrome, and antiphospholipid antibodies. Front Biosci 12 (2007) 2171–2182.PubMedCrossRefGoogle Scholar
  76. Nirmalananthan, N. and Greensmith, L. Amyotrophic lateral sclerosis: Recent advances and future therapies. Curr Opin Neurol 18 (2005) 712–719.PubMedCrossRefGoogle Scholar
  77. Oddo, S., Billings, L., Kesslak, J. P., Cribbs, D. H. and LaFerla, F. M. Aβ immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome. Neuron 43 (2004) 321–332.PubMedCrossRefGoogle Scholar
  78. Oei, H.-H. S., van der Meer, I. M., Hofman, A., Koudstaal, P. J., Stijnen, T., Breteler, M. M. B. and Witteman, J. C. M. Lipoprotein-associated phospholipase A2 activity is associated with risk of coronary heart disease and ischemic stroke: The Rotterdam study. Circulation 111 (2005) 570–575.PubMedCrossRefGoogle Scholar
  79. Pacher, P., Batkai, S. and Kunos, G. ,The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58 (2006) 389–462.PubMedCrossRefGoogle Scholar
  80. Papandreou, D., Pavlou, E., Kalimeri, E. and Mavromichalis, I. The ketogenic diet in children with epilepsy. Br J Nutr 95 (2006) 5–13.PubMedCrossRefGoogle Scholar
  81. Piomelli, D., Astarita, G. and Rapaka, R. A neuroscientist's guide to lipidomics. Nat Rev Neurosci 8 (2007) 743–754.PubMedCrossRefGoogle Scholar
  82. Puglielli, L. Aging of the brain, neurotrophin signaling, and Alzheimer's disease: Is IGF1-R the common culprit? Neurobiol Aging (2007) doi:10.1016/j.neurobiolaging.2007.01.010.Google Scholar
  83. Puri, B. K., Leavitt, B. R., Hayden, M. R., Ross, C. A., Rosenblatt, A., Greenamyre, J. T., Hersch, S., Vaddadi, K. S., Sword, A., Horrobin, D. F., Manku, M. and Murck, H. Ethyl-EPA in Huntington disease: A double-blind, randomized, placebo-controlled trial. Neurology 65 (2005) 286–292.PubMedCrossRefGoogle Scholar
  84. Qin, J., Goswami, R., Balabanov, R. and Dawson, G. Oxidized phosphatidylcholine is a marker for neuroinflammation in multiple sclerosis brain. J Neurosci Res 85 (2007) 977–984.PubMedCrossRefGoogle Scholar
  85. Reid, P. C., Sakashita, N., Sugii, S., Ohno-Iwashita, Y., Shimada, Y., Hickey, W. F. and Chang, T.-Y. A novel cholesterol stain reveals early neuronal cholesterol accumulation in the Niemann-Pick type C1 mouse brain. J Lipid Res 45 (2004) 582–591.PubMedCrossRefGoogle Scholar
  86. Rigg, J. L. and Zafonte, R. D. Corticosteroids in TBI: Is the story closed? J Head Trauma Rehab 21 (2006) 285–288.Google Scholar
  87. Samadi, P., Grégoire, L., Rouillard, C., Bédard, P. J., Di Paolo, T. and Lévesque, D. Docosahexaenoic acid reduces levodopa-induced dyskinesias in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkeys. Ann Neurol 59 (2006) 282–288.PubMedCrossRefGoogle Scholar
  88. Sayeed, I., Guo, Q., Hoffman, S. W. and Stein, D. G. Allopregnanolone, a progesterone metabolite, is more effective than progesterone in reducing cortical infarct volume after transient middle cerebral artery occlusion. Ann Emerg Med 47 (2006) 381–389.PubMedCrossRefGoogle Scholar
  89. Schuchman, E. The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann–Pick disease. J Inher Metabol Dis 30 (2007) 654–663.CrossRefGoogle Scholar
  90. Schwab, C., Hosokawa, M. and McGeer, P. L. Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease. Exp Neurol 188 (2004) 52–64.PubMedCrossRefGoogle Scholar
  91. Serhan, C. N. Resolution phases of inflammation: Novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Ann Rev Immunol 25 (2007) 101–137.CrossRefGoogle Scholar
  92. Sharon, R., Bar-Joseph, I., Frosch, M. P., Walsh, D. M., Hamilton, J. A. and Selkoe, D. J. The formation of highly soluble oligomers of α-synuclein is regulated by fatty acids and enhanced in Parkinson's disease. Neuron 37 (2003) 583–595.PubMedCrossRefGoogle Scholar
  93. Simmons, D. L., Botting, R. M. and Hla, T. Cyclooxygenase isozymes: The biology of prostaglandin synthesis and inhibition. Pharmacol Rev 56 (2004) 387–437.PubMedCrossRefGoogle Scholar
  94. Simpson, E. P., Henry, Y. K., Henkel, J. S., Smith, R. G. and Appel, S. H. Increased lipid peroxidation in sera of ALS patients: A potential biomarker of disease burden. Neurology 62 (2004) 1758–1765.PubMedGoogle Scholar
  95. Smith, C., Graham, D. I., Murray, L. S., Stewart, J. and Nicoll, J. A. R. Association of APOE e4 and cerebrovascular pathology in traumatic brain injury. J Neurol Neurosurg Psychiatry 77 (2006) 363–366.PubMedCrossRefGoogle Scholar
  96. Stack, E. C., Smith, K. M., Ryu, H., Cormier, K., Chen, M., Hagerty, S. W., Del Signore, S. J., Cudkowicz, M. E., Friedlander, R. M. and Ferrante, R. J. Combination therapy using minocycline and coenzyme Q10 in R6/2 transgenic Huntington's disease mice. Biochim Biophys Acta 1762 (2006) 373–380.PubMedGoogle Scholar
  97. Stoll, G. and Bendszus, M. Inflammation and atherosclerosis: Novel insights into plaque formation and destabilization. Stroke 37 (2006) 1923–1932.PubMedCrossRefGoogle Scholar
  98. Suzuki, M., Wright, L. S., Marwah, P., Lardy, H. A. and Svendsen, C. N. Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural stem cell cultures derived from the fetal cortex. Proc Natl Acad Sci USA 101 (2004) 3202–3207.PubMedCrossRefGoogle Scholar
  99. Temel, R. E., Tang, W., Ma, Y., Rudel, L. L., Willingham, M. C., Ioannou, Y. A., Davies, J. P., Nilsson, L.-M. and Yu, L. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe. J Clin Invest 117 (2007) 1968–1978.PubMedCrossRefGoogle Scholar
  100. Vance, J. E. Lipid imbalance in the neurological disorder, Niemann-Pick C disease. FEBS Lett 580 (2006) 5518–5524.PubMedCrossRefGoogle Scholar
  101. Wang, J. M., Johnston, P. B., Ball, B. G. and Brinton, R. D. The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates cell-cycle gene and protein expression. J Neurosci 25 (2005) 4706–4718.PubMedCrossRefGoogle Scholar
  102. Wang, J. M., Liu, L., Irwin, R. W., Chen, S. and Brinton, R. D. Regenerative potential of allopregnanolone. Brain Res Rev (2007a) In press: doi:10.1016/j.brainresrev.2007.08.010.Google Scholar
  103. Wang, Q., Tang, X. N. and Yenari, M. A. The inflammatory response in stroke. J Neuroimmunol 184 (2007b) 53–68.CrossRefGoogle Scholar
  104. Welch, K. and Yuan, J. α-Synuclein oligomerization: A role for lipids? Trends Neurosci 26 (2003) 517–519.PubMedCrossRefGoogle Scholar
  105. Whitfield, J. F. Can statins put the brakes on Alzheimer's disease? Expert Opin Investig Drugs 15 (2006) 1479–1485.PubMedCrossRefGoogle Scholar
  106. Williams, T. I., Lynn, B. C., Markesbery, W. R. and Lovell, M. A. Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in mild cognitive impairment and early Alzheimer's disease. Neurobiol Aging 27 (2006) 1094–1099.PubMedCrossRefGoogle Scholar
  107. Wojtal, K., Trojnar, M. K. and Czuczwar, S. J. Endogenous neuroprotective factors: Neurosteroids. Pharmacol Reports 58 (2006) 335–340.Google Scholar
  108. Xie, C., Burns, D. K., Turley, S. D. and Dietschy, J. M. Cholesterol is sequestered in the brains of mice with Niemann-Pick type C disease but turnover is increased. J Neuropathol Exp Neurol 59 (2000) 1106–1117.PubMedGoogle Scholar
  109. Young, A. R., Ali, C., Duretete, A. and Vivien, D. Neuroprotection and stroke: Time for a compromise. J Neurochem 103 (2007) 1302–1309.PubMedCrossRefGoogle Scholar
  110. Zalewski, A., Nelson, J. J., Hegg, L. and Macphee, C. Lp-PLA2: A new kid on the block. Clin Chem 52 (2006) 1645–1650.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Rao Muralikrishna Adibhatla
    • 1
  • J. F. Hatcher
  1. 1.Department of Neurological Surgery, Cardiovascular Research Center, Neuroscience Training ProgramUniversity of Wisconsin School of Medicine and Public Health, Madison, WI., William S. Middleton Veterans Affairs HospitalMadisonUSA

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