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Distinct Roles of Cyclooxygenase-1 and Cyclooxygenase-2 in Inflammatory and Excitotoxic Brain Injury

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Oxidative Stress and Free Radical Damage in Neurology

Abstract

The cyclooxygenases COX-1 and COX-2 metabolize arachidonic acid to prostaglandins (PGs) and thromboxanes and are thought to play a role in neuroinflammation and excitotoxicity, which are important components in the progression of neurodegenerative diseases. However, the exact role of each isoform in these processes remains unclear. This chapter reviews preclinical and clinical data on COX-1 and COX-2 inhibition in the neuroinflammatory and excitotoxic processes. Potential implications for clinical use in patients suffering from neurodegenerative disorders with a marked inflammatory component, such as Alzheimer’s disease, are discussed.

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References

  1. Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem. 2000;69:145–82.

    Article  CAS  PubMed  Google Scholar 

  2. Bazan NG, Colangelo V, Lukiw WJ. Prostaglandins and other lipid mediators in Alzheimer’s disease. Prostaglandins Other Lipid Mediat. 2002;68-69:197–210.

    Article  CAS  PubMed  Google Scholar 

  3. Candelario-Jalil E, Fiebich BL. Cyclooxygenase inhibition in ischemic brain injury. Curr Pharm Des. 2008;14:1401–18.

    Article  CAS  PubMed  Google Scholar 

  4. Hoozemans JJ, Rozemuller JM, van Haastert ES, Veerhuis R, Eikelenboom P. Cyclooxygenase-1 and -2 in the different stages of Alzheimer’s disease pathology. Curr Pharm Des. 2008;14:1419–27.

    Article  CAS  PubMed  Google Scholar 

  5. Asanuma M, Miyazaki I. Nonsteroidal anti-inflammatory drugs in experimental parkinsonian models and Parkinson’s disease. Curr Pharm Des. 2008;14:1428–34.

    Article  CAS  PubMed  Google Scholar 

  6. Wenk GL. Neuropathologic changes in Alzheimer’s disease. J Clin Psychiatry. 2003;64 Suppl. 9:7–10.

    PubMed  Google Scholar 

  7. Hunot S, Hirsch E.C. Neuroinflammatory processes in Parkinson’s disease. Ann Neurol. 2003;53 Suppl. 3:S49–58; discussion S-60.

    Article  CAS  PubMed  Google Scholar 

  8. Mhatre M, Floyd RA, Hensley K. Oxidative stress and neuroinflammation in Alzheimer’s disease and amyotrophic lateral sclerosis: common links and potential therapeutic targets. J Alzheimers Dis. 2004;6:147–57.

    CAS  PubMed  Google Scholar 

  9. Morita I, Schindler M, Regier MK, et al. Different intracellular locations for prostaglandin endoperoxide H synthase-1 and -2. J Biol Chem. 1995;270:10902–8.

    Article  CAS  PubMed  Google Scholar 

  10. Breder CD. Cyclooxygenase systems in the mammalian brain. Ann N Y Acad Sci. 1997;813:296–301.

    Article  CAS  PubMed  Google Scholar 

  11. Murakami M, Kudo I. Recent advances in molecular biology and physiology of the prostaglandin E2-biosynthetic pathway. Prog Lipid Res. 2004;43:3–35.

    Article  CAS  PubMed  Google Scholar 

  12. Ueno N, Takegoshi Y, Kamei D, Kudo I, Murakami M. Coupling between cyclooxygenases and terminal prostanoid synthases. Biochem Biophys Res Commun. 2005;338:70–6.

    Article  CAS  PubMed  Google Scholar 

  13. Morita I. Distinct functions of COX-1 and COX-2. Prostaglandins Other Lipid Mediat. 2002;68–69:165–75.

    Article  PubMed  Google Scholar 

  14. Kang YJ, Mbonye UR, DeLong CJ, Wada M, Smith WL. Regulation of intracellular cyclooxygenase levels by gene transcription and protein degradation. Prog Lipid Res. 2007;46:108–25.

    Article  CAS  PubMed  Google Scholar 

  15. Tomimoto H, Shibata M, Ihara M, Akiguchi I, Ohtani R, Budka H. A comparative study on the expression of cyclooxygenase and 5-lipoxygenase during cerebral ischemia in humans. Acta Neuropathol. 2002;104:601–7.

    CAS  PubMed  Google Scholar 

  16. Breder CD, Dewitt D, Kraig RP. Characterization of inducible cyclooxygenase in rat brain. J Comp Neurol. 1995;355:296–315.

    Article  CAS  PubMed  Google Scholar 

  17. Li S, Wang Y, Matsumura K, Ballou LR, Morham SG, Blatteis CM. The febrile response to lipopolysaccharide is blocked in cyclooxygenase-2(–/–), but not in cyclooxygenase-1(–/–) mice. Brain Res. 1999;825:86–94.

    Article  CAS  PubMed  Google Scholar 

  18. Yermakova AV, Rollins J, Callahan LM, Rogers J, O’Banion MK. Cyclooxygenase-1 in human Alzheimer and control brain: quantitative analysis of expression by microglia and CA3 hippocampal neurons. J Neuropathol Exp Neurol. 1999;58:1135–46.

    Article  CAS  PubMed  Google Scholar 

  19. Deininger MH, Meyermann R, Trautmann K, et al. Cyclooxygenase (COX)-1 expressing macrophages/microglial cells and COX-2 expressing astrocytes accumulate during oligodendroglioma progression. Brain Res. 2000;885:111–6.

    Article  CAS  PubMed  Google Scholar 

  20. Kroin JS, Takatori M, Li J, Chen EY, Buvanendran A, Tuman KJ. Upregulation of dorsal horn microglial cyclooxygenase-1 and neuronal cyclooxygenase-2 after thoracic deep muscle incisions in the rat. Anesth Analg. 2008;106:1288–95, table of contents.

    Article  CAS  PubMed  Google Scholar 

  21. Kaufmann WE, Andreasson KI, Isakson PC, Worley PF. Cyclooxygenases and the central nervous system. Prostaglandins. 1997;54:601–24.

    Article  CAS  PubMed  Google Scholar 

  22. Phillis JW, Horrocks LA, Farooqui AA. Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: their role and involvement in neurological disorders. Brain Res Brain Res Rev. 2006;52:201–43.

    Article  CAS  Google Scholar 

  23. Schwab JM, Beschorner R, Meyermann R, Gozalan F, Schluesener HJ. Persistent accumulation of cyclooxygenase-1-expressing microglial cells and macrophages and transient upregulation by endothelium in human brain injury. J Neurosurg. 2002;96:892–9.

    Article  CAS  PubMed  Google Scholar 

  24. Choi SH, Langenbach R, Bosetti F. Genetic deletion or pharmacological inhibition of cyclooxygenase-1 attenuate lipopolysaccharide-induced inflammatory response and brain injury. FASEB J. 2008;22:1491–501.

    Article  CAS  PubMed  Google Scholar 

  25. Hayaishi O, Matsumura H. Prostaglandins and sleep. Adv Neuroimmunol. 1995;5:211–6.

    Article  CAS  PubMed  Google Scholar 

  26. Minghetti L. Role of COX-2 in inflammatory and degenerative brain diseases. Subcell Biochem. 2007;42:127–41.

    Article  PubMed  Google Scholar 

  27. Kaufmann WE, Worley PF, Pegg J, Bremer M, Isakson P. COX-2, a synaptically induced enzyme, is expressed by excitatory neurons at postsynaptic sites in rat cerebral cortex. Proc Natl Acad Sci USA. 1996;93:2317–21.

    Article  CAS  PubMed  Google Scholar 

  28. Stefanovic B, Bosetti F, Silva AC. Modulatory role of cyclooxygenase-2 in cerebrovascular coupling. Neuroimage. 2006;32:23–32.

    Article  PubMed  Google Scholar 

  29. Ojeda SR, Urbanski HF, Junier MP, Capdevila J. The role of arachidonic acid and its metabolites in the release of neuropeptides. Ann N Y Acad Sci. 1989;559:192–207.

    Article  CAS  PubMed  Google Scholar 

  30. Cowley TR, Fahey B, O’Mara SM. COX-2, but not COX-1, activity is necessary for the induction of perforant path long-term potentiation and spatial learning in vivo. Eur J Neurosci. 2008.

    Google Scholar 

  31. Seibert K, Zhang Y, Leahy K, et al. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci USA. 1994;91:12013–7.

    Article  CAS  PubMed  Google Scholar 

  32. Yasojima K, Schwab C, McGeer EG, McGeer PL. Distribution of cyclooxygenase-1 and cyclooxygenase-2 mRNAs and proteins in human brain and peripheral organs. Brain Res. 1999;830:226–36.

    Article  CAS  PubMed  Google Scholar 

  33. Yamagata K, Andreasson KI, Kaufmann WE, Barnes CA, Worley PF. Expression of a mitogen-inducible cyclooxygenase in brain neurons: regulation by synaptic activity and glucocorticoids. Neuron. 1993;11:371–86.

    Article  CAS  PubMed  Google Scholar 

  34. Chen C, Magee JC, Bazan NG. Cyclooxygenase-2 regulates prostaglandin E2 signaling in hippocampal long-term synaptic plasticity. J Neurophysiol. 2002;87:2851–7.

    CAS  PubMed  Google Scholar 

  35. Rall JM, Mach SA, Dash PK. Intrahippocampal infusion of a cyclooxygenase-2 inhibitor attenuates memory acquisition in rats. Brain Res. 2003;968:273–6.

    Article  CAS  PubMed  Google Scholar 

  36. Teather LA, Packard MG, Bazan NG. Post-training cyclooxygenase-2 (COX-2) inhibition impairs memory consolidation. Learn Mem. 2002;9:41–7.

    Article  PubMed  Google Scholar 

  37. Sato T, Ishida T, Irifune M, et al. Effect of NC-1900, an active fragment analog of arginine vasopressin, and inhibitors of arachidonic acid metabolism on performance of a passive avoidance task in mice. Eur J Pharmacol. 2007;560:36–41.

    Article  CAS  PubMed  Google Scholar 

  38. Holscher C. Inhibitors of cyclooxygenases produce amnesia for a passive avoidance task in the chick. Eur J Neurosci. 1995;7:1360–5.

    Article  CAS  PubMed  Google Scholar 

  39. Sharifzadeh M, Tavasoli M, Soodi M, Mohammadi-Eraghi S, Ghahremani MH, Roghani A. A time course analysis of cyclooxygenase-2 suggests a role in spatial memory retrieval in rats. Neurosci Res. 2006;54:171–9.

    Article  CAS  PubMed  Google Scholar 

  40. Candelario-Jalil E, Gonzalez-Falcon A, Garcia-Cabrera M, et al. Assessment of the relative contribution of COX-1 and COX-2 isoforms to ischemia-induced oxidative damage and neurodegeneration following transient global cerebral ischemia. J Neurochem. 2003;86:545–55.

    Article  CAS  PubMed  Google Scholar 

  41. Pepicelli O, Fedele E, Berardi M, et al. Cyclo-oxygenase-1 and -2 differently contribute to prostaglandin E2 synthesis and lipid peroxidation after in vivo activation of N-methyl-d-aspartate receptors in rat hippocampus. J Neurochem. 2005;93:1561–7.

    Article  CAS  PubMed  Google Scholar 

  42. Bruce-Keller AJ. Microglial-neuronal interactions in synaptic damage and recovery. J Neurosci Res. 1999;58:191–201.

    Article  CAS  PubMed  Google Scholar 

  43. Streit WJ. Microglia as neuroprotective, immunocompetent cells of the CNS. Glia. 2002;40:133–9.

    Article  PubMed  Google Scholar 

  44. Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996;19:312–8.

    Article  CAS  PubMed  Google Scholar 

  45. Nelson PT, Soma LA, Lavi E. Microglia in diseases of the central nervous system. Ann Med. 2002;34:491–500.

    Article  CAS  PubMed  Google Scholar 

  46. Stence N, Waite M, Dailey ME. Dynamics of microglial activation: a confocal time-lapse analysis in hippocampal slices. Glia. 2001;33:256–66.

    Article  CAS  PubMed  Google Scholar 

  47. Block ML, Zecca L, Hong JS. Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci. 2007;8:57–69.

    Article  CAS  PubMed  Google Scholar 

  48. Hata AN, Breyer RM. Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation. Pharmacol Ther. 2004;103:147–66.

    Article  CAS  PubMed  Google Scholar 

  49. Liberatore GT, Jackson-Lewis V, Vukosavic S, et al. Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med. 1999;5:1403–9.

    Article  CAS  PubMed  Google Scholar 

  50. Dehmer T, Lindenau J, Haid S, Dichgans J, Schulz JB. Deficiency of inducible nitric oxide synthase protects against MPTP toxicity in vivo. J Neurochem. 2000;74:2213–6.

    Article  CAS  PubMed  Google Scholar 

  51. Aid S, Langenbach R, Bosetti F. Neuroinflammatory response to lipopolysaccharide is exacerbated in mice genetically deficient in cyclooxygenase-2. J Neuroinflammation. 2008;5:17.

    Article  PubMed  CAS  Google Scholar 

  52. Xie Z, Wei M, Morgan TE, et al. Peroxynitrite mediates neurotoxicity of amyloid beta-peptide1–42- and lipopolysaccharide-activated microglia. J Neurosci. 2002;22:3484–92.

    CAS  PubMed  Google Scholar 

  53. McGeer PL, Itagaki S, Tago H, McGeer EG. Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR. Neurosci Lett. 1987;79:195–200.

    Article  CAS  PubMed  Google Scholar 

  54. Streit WJ, Mrak RE, Griffin WS. Microglia and neuroinflammation: a pathological perspective. J Neuroinflammation. 2004;1:14.

    Article  PubMed  CAS  Google Scholar 

  55. McGeer PL, McGeer EG. Inflammation and the degenerative diseases of aging. Ann N Y Acad Sci. 2004;1035:104–16.

    Article  CAS  PubMed  Google Scholar 

  56. Heneka MT, O’Banion MK. Inflammatory processes in Alzheimer’s disease. J Neuroimmunol. 2007;184:69–91.

    Article  CAS  PubMed  Google Scholar 

  57. Fiala M, Liu QN, Sayre J, et al. Cyclooxygenase-2-positive macrophages infiltrate the Alzheimer’s disease brain and damage the blood-brain barrier. Eur J Clin Invest. 2002;32:360–71.

    Article  CAS  PubMed  Google Scholar 

  58. Matsumoto Y, Yanase D, Noguchi-Shinohara M, Ono K, Yoshita M, Yamada M. Blood-brain barrier permeability correlates with medial temporal lobe atrophy but not with amyloid-beta protein transport across the blood-brain barrier in Alzheimer’s disease. Dement Geriatr Cogn Disord. 2007;23:241–5.

    Article  CAS  PubMed  Google Scholar 

  59. McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology. 1996;47:425–32.

    CAS  PubMed  Google Scholar 

  60. Breitner JC, Welsh KA, Helms MJ, et al. Delayed onset of Alzheimer’s disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs. Neurobiol Aging. 1995;16:523–30.

    Article  CAS  PubMed  Google Scholar 

  61. Rich JB, Rasmusson DX, Folstein MF, Carson KA, Kawas C, Brandt J. Nonsteroidal anti-inflammatory drugs in Alzheimer’s disease. Neurology. 1995;45:51–5.

    CAS  PubMed  Google Scholar 

  62. McGeer PL, McGeer EG. NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies. Neurobiol Aging. 2007;28:639–47.

    Article  CAS  PubMed  Google Scholar 

  63. Rogers J, Kirby LC, Hempelman SR, et al. Clinical trial of indomethacin in Alzheimer’s disease. Neurology. 1993;43:1609–11.

    CAS  PubMed  Google Scholar 

  64. Scharf S, Mander A, Ugoni A, Vajda F, Christophidis N. A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer’s disease. Neurology. 1999;53:197–201.

    CAS  PubMed  Google Scholar 

  65. Aisen PS, Schafer KA, Grundman M, et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA. 2003;289:2819–26.

    Article  CAS  PubMed  Google Scholar 

  66. Aisen PS, Schmeidler J, Pasinetti GM. Randomized pilot study of nimesulide treatment in Alzheimer’s disease. Neurology. 2002;58:1050–4.

    CAS  PubMed  Google Scholar 

  67. Reines SA, Block GA, Morris JC, et al. Rofecoxib: no effect on Alzheimer’s disease in a 1-year, randomized, blinded, controlled study. Neurology. 2004;62:66–71.

    CAS  PubMed  Google Scholar 

  68. Group AR, Lyketsos CG, Breitner JC, et al. Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial. Neurology. 2007;68:1800–8.

    Article  CAS  Google Scholar 

  69. Soininen H, West C, Robbins J, Niculescu L. Long-term efficacy and safety of celecoxib in Alzheimer’s disease. Dement Geriatr Cogn Disord. 2007;23:8–21.

    Article  CAS  PubMed  Google Scholar 

  70. Thal LJ, Ferris SH, Kirby L, et al. A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment. Neuropsychopharmacology. 2005;30:1204–15.

    Article  CAS  PubMed  Google Scholar 

  71. Psaty BM, Kronmal RA. Reporting mortality findings in trials of rofecoxib for Alzheimer disease or cognitive impairment: a case study based on documents from rofecoxib litigation. JAMA. 2008;299:1813–7.

    Article  CAS  PubMed  Google Scholar 

  72. Kukar T, Murphy MP, Eriksen JL, et al. Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Abeta42 production. Nat Med. 2005;11:545–50.

    Article  CAS  PubMed  Google Scholar 

  73. Weggen S, Eriksen JL, Das P, et al. A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature. 2001;414:212–6.

    Article  CAS  PubMed  Google Scholar 

  74. Szekely CA, Green RC, Breitner JC, et al. No advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology. 2008;70:2291–8.

    Article  CAS  PubMed  Google Scholar 

  75. Sastre M, Dewachter I, Rossner S, et al. Nonsteroidal anti-inflammatory drugs repress beta-secretase gene promoter activity by the activation of PPARgamma. Proc Natl Acad Sci USA. 2006;103:443–8.

    Article  CAS  PubMed  Google Scholar 

  76. Heneka MT, Landreth GE. PPARs in the brain. Biochim Biophys Acta. 2007;1771:1031–45.

    CAS  PubMed  Google Scholar 

  77. Teismann P, Ferger B. Inhibition of the cyclooxygenase isoenzymes COX-1 and COX-2 provide neuroprotection in the MPTP-mouse model of Parkinson’s disease. Synapse. 2001;39:167–74.

    Article  CAS  PubMed  Google Scholar 

  78. Portanova JP, Zhang Y, Anderson GD, et al. Selective neutralization of prostaglandin E2 blocks inflammation, hyperalgesia, and interleukin 6 production in vivo. J Exp Med. 1996;184:883–91.

    Article  CAS  PubMed  Google Scholar 

  79. Teismann P, Tieu K, Choi DK, et al. Cyclooxygenase-2 is instrumental in Parkinson’s disease neurodegeneration. Proc Natl Acad Sci USA. 2003;100:5473–8.

    Article  CAS  PubMed  Google Scholar 

  80. Aid S, Bosetti F. Gene expression of cyclooxygenase-1 and Ca(2+)-independent phospholipase A(2) is altered in rat hippocampus during normal aging. Brain Res Bull. 2007;73:108–13.

    Article  CAS  PubMed  Google Scholar 

  81. Hoozemans JJ, Veerhuis R, Janssen I, van Elk EJ, Rozemuller AJ, Eikelenboom P. The role of cyclo-oxygenase 1 and 2 activity in prostaglandin E(2) secretion by cultured human adult microglia: implications for Alzheimer’s disease. Brain Res. 2002;951:218–26.

    Article  CAS  PubMed  Google Scholar 

  82. Candelario-Jalil E, de Oliveira AC, Graf S, et al. Resveratrol potently reduces prostaglandin E2 production and free radical formation in lipopolysaccharide-activated primary rat microglia. J Neuroinflammation. 2007;4:25.

    Article  PubMed  CAS  Google Scholar 

  83. Xia Y, Yamagata K, Krukoff TL. Differential expression of the CD14/TLR4 complex and inflammatory signaling molecules following i.c.v. administration of LPS. Brain Res. 2006;1095:85–95.

    Article  CAS  PubMed  Google Scholar 

  84. Veszelka S, Urbanyi Z, Pazmany T, et al. Human serum amyloid P component attenuates the bacterial lipopolysaccharide-induced increase in blood-brain barrier permeability in mice. Neurosci Lett. 2003;352:57–60.

    Article  CAS  PubMed  Google Scholar 

  85. Tomas-Camardiel M, Venero JL, Herrera AJ, et al. Blood–brain barrier disruption highly induces aquaporin-4 mRNA and protein in perivascular and parenchymal astrocytes: protective effect by estradiol treatment in ovariectomized animals. J Neurosci Res. 2005;80:235–46.

    Article  CAS  PubMed  Google Scholar 

  86. Rosenberg GA, Estrada EY, Mobashery S. Effect of synthetic matrix metalloproteinase inhibitors on lipopolysaccharide-induced blood-brain barrier opening in rodents: differences in response based on strains and solvents. Brain Res. 2007;1133:186–92.

    Article  CAS  PubMed  Google Scholar 

  87. Jaworowicz DJ Jr, Korytko PJ, Singh Lakhman S, Boje KM. Nitric oxide and prostaglandin E2 formation parallels blood-brain barrier disruption in an experimental rat model of bacterial meningitis. Brain Res Bull. 1998;46:541–6.

    Article  CAS  PubMed  Google Scholar 

  88. Candelario-Jalil E, Taheri S, Yang Y, et al. Cyclooxygenase inhibition limits blood-brain barrier disruption following intracerebral injection of tumor necrosis factor-alpha in the rat. J Pharmacol Exp Ther. 2007;323:488–98.

    Article  CAS  PubMed  Google Scholar 

  89. Pu H, Hayashi K, Andras IE, Eum SY, Hennig B, Toborek M. Limited role of COX-2 in HIV Tat-induced alterations of tight junction protein expression and disruption of the blood-brain barrier. Brain Res. 2007;1184:333–44.

    Article  CAS  PubMed  Google Scholar 

  90. de Vries HE, Blom-Roosemalen MC, van Oosten M, et al. The influence of cytokines on the integrity of the blood-brain barrier in vitro. J Neuroimmunol. 1996;64:37–43.

    Article  CAS  PubMed  Google Scholar 

  91. Toscano CD, Ueda Y, Tomita YA, Vicini S, Bosetti F. Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice. Brain Res Bull. 2008;75:598–609.

    Article  CAS  PubMed  Google Scholar 

  92. Baik EJ, Kim EJ, Lee SH, Moon C. Cyclooxygenase-2 selective inhibitors aggravate kainic acid induced seizure and neuronal cell death in the hippocampus. Brain Res. 1999;843:118–29.

    Article  CAS  PubMed  Google Scholar 

  93. Tuo J, Tuaillon N, Shen D, Chan CC. Endotoxin-induced uveitis in cyclooxygenase-2-deficient mice. Invest Ophthalmol Vis Sci. 2004;45:2306–13.

    Article  PubMed  Google Scholar 

  94. Blais V, Turrin NP, Rivest S. Cyclooxygenase 2 (COX-2) inhibition increases the inflammatory response in the brain during systemic immune stimuli. J Neurochem. 2005;95:1563–74.

    Article  CAS  PubMed  Google Scholar 

  95. Gu B, Desjardins P, Butterworth RF. Selective increase of neuronal cyclooxygenase-2 (COX-2) expression in vulnerable brain regions of rats with experimental Wernicke’s encephalopathy: effect of nimesulide. Metab Brain Dis. 2008.

    Google Scholar 

  96. Germann B, Neuhaus W, Hofer-Warbinek R, Noe CR. Applying blood–brain barrier in vitro models to study the influence of drugs on endothelial cells: effects of selected COX-inhibitors. Pharmazie. 2008;63:303–7.

    CAS  PubMed  Google Scholar 

  97. Shie FS, Montine KS, Breyer RM, Montine TJ. Microglial EP2 is critical to neurotoxicity from activated cerebral innate immunity. Glia. 2005;52:70–7.

    Article  PubMed  Google Scholar 

  98. Sugimoto Y, Narumiya S. Prostaglandin E receptors. J Biol Chem. 2007;282:11613–7.

    Article  CAS  PubMed  Google Scholar 

  99. Yamane H, Sugimoto Y, Tanaka S, Ichikawa A. Prostaglandin E(2) receptors, EP2 and EP4, differentially modulate TNF-alpha and IL-6 production induced by lipopolysaccharide in mouse peritoneal neutrophils. Biochem Biophys Res Commun. 2000;278:224–8.

    Article  CAS  PubMed  Google Scholar 

  100. Serhan CN, Chiang N. Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus. Br J Pharmacol. 2008;153(:uppl 1):S200–15.

    CAS  PubMed  Google Scholar 

  101. Gilroy DW, Colville-Nash PR, Willis D, Chivers J, Paul-Clark MJ, Willoughby DA. Inducible cyclooxygenase may have anti-inflammatory properties. Nat Med. 1999;5:698–701.

    Article  CAS  PubMed  Google Scholar 

  102. Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol. 2008;8:349–61.

    Article  CAS  PubMed  Google Scholar 

  103. Kozak KR, Crews BC, Morrow JD, et al. Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. J Biol Chem. 2002;277:44877–85.

    Article  CAS  PubMed  Google Scholar 

  104. Wolf SA, Ullrich O. Endocannabinoids and the brain immune system: new neurones at the horizon? J Neuroendocrinol. 2008;20 Suppl. 1:15–9.

    Article  CAS  PubMed  Google Scholar 

  105. Bosetti F. Arachidonic acid metabolism in brain physiology and pathology: lessons from genetically altered mouse models. J Neurochem. 2007.

    Google Scholar 

  106. Scali C, Prosperi C, Vannucchi MG, Pepeu G, Casamenti F. Brain inflammatory reaction in an animal model of neuronal degeneration and its modulation by an anti-inflammatory drug: implication in Alzheimer’s disease. Eur J Neurosci. 2000;12:1900–12.

    Article  CAS  PubMed  Google Scholar 

  107. Iadecola C, Niwa K, Nogawa S, et al. Reduced susceptibility to ischemic brain injury and N-methyl-d-aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice. Proc Natl Acad Sci USA. 2001;98:1294–9.

    Article  CAS  PubMed  Google Scholar 

  108. Hewett SJ, Silakova JM, Hewett JA. Oral treatment with rofecoxib reduces hippocampal excitotoxic neurodegeneration. J Pharmacol Exp Ther. 2006;319:1219–24.

    Article  CAS  PubMed  Google Scholar 

  109. Candelario-Jalil E, Ajamieh HH, Sam S, Martinez G, Leon Fernandez OS. Nimesulide limits kainate-induced oxidative damage in the rat hippocampus. Eur J Pharmacol. 2000;390:295–8.

    Article  CAS  PubMed  Google Scholar 

  110. Kunz T, Oliw EH. Nimesulide aggravates kainic acid-induced seizures in the rat. Pharmacol Toxicol. 2001;88:271–6.

    Article  CAS  PubMed  Google Scholar 

  111. Kunz T, Oliw EH. The selective cyclooxygenase-2 inhibitor rofecoxib reduces kainate-induced cell death in the rat hippocampus. Eur J Neurosci. 2001;13:569–75.

    Article  CAS  PubMed  Google Scholar 

  112. Ciceri P, Zhang Y, Shaffer AF, et al. Pharmacology of celecoxib in rat brain after kainate administration. J Pharmacol Exp Ther. 2002;302:846–52.

    Article  CAS  PubMed  Google Scholar 

  113. Gobbo OL, O’Mara SM. Post-treatment, but not pre-treatment, with the selective cyclooxygenase-2 inhibitor celecoxib markedly enhances functional recovery from kainic acid-induced neurodegeneration. Neuroscience. 2004;125:317–27.

    Article  CAS  PubMed  Google Scholar 

  114. Wang Q, Yu S, Simonyi A, Sun GY, Sun AY. Kainic acid-mediated excitotoxicity as a model for neurodegeneration. Mol Neurobiol. 2005;31:3–16.

    Article  CAS  PubMed  Google Scholar 

  115. Sattler R, Tymianski M. Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death. Mol Neurobiol. 2001;24:107–29.

    Article  CAS  PubMed  Google Scholar 

  116. Tu B, Bazan NG. Hippocampal kindling epileptogenesis upregulates neuronal cyclooxygenase-2 expression in neocortex. Exp Neurol. 2003;179:167–75.

    Article  CAS  PubMed  Google Scholar 

  117. Yoshikawa K, Kita Y, Kishimoto K, Shimizu T. Profiling of eicosanoid production in the rat hippocampus during kainate-induced seizure: dual-phase regulation and differential involvement of cox-1 and cox-2. J Biol Chem. 2006.

    Google Scholar 

  118. Toscano CD, Prabhu VV, Langenbach R, Becker KG, Bosetti F. Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain. Genome Biol. 2007;8:R14.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA

    Francesca Bosetti

Authors
  1. Saba A¨d
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  2. Sang-Ho Choi
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  3. Christopher D. Toscano
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  4. Francesca Bosetti
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Correspondence to Francesca Bosetti .

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Editors and Affiliations

  1. Medical School, Dept. Neurology, Tel Aviv University, Tel Aviv, 69978, Israel

    Natan Gadoth

  2. Neurochirurgische Klinik, Abt. Neuropathologie, Universitätsklinikum Mainz, Langenbeckstr. 1, Mainz, 55131, Germany

    Hans Hilmar Göbel

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A¨d, S., Choi, SH., Toscano, C.D., Bosetti, F. (2011). Distinct Roles of Cyclooxygenase-1 and Cyclooxygenase-2 in Inflammatory and Excitotoxic Brain Injury. In: Gadoth, N., Göbel, H. (eds) Oxidative Stress and Free Radical Damage in Neurology. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press. https://doi.org/10.1007/978-1-60327-514-9_8

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