Non-steroidal anti-inflammatory drugs in alzheimer's disease and parkinson's disease: Reconsidering the role of neuroinflammation

Pharmaceuticals

Volumn 3, Issue 6, 2010, Pages 1812-1841

  Moore, Amy H ^a   Bigbee, Matthew J ^a   Boynton, Grace E ^a   Wakeham, Colin M ^a   Rosenheim, Hilary M ^a   Staral, Christopher J ^a   Morrissey, James L ^a   Hund, Amanda K ^a  

^a CARLETON COLLEGE   (United States)

Author keywords

Alzheimer's disease; Cyclooxygenase; Neuroinflammation; Non steroidal anti inflammatory drugs; Parkinson's disease

Indexed keywords

5 BROMO 2 (4 FLUOROPHENYL) 3 (4 METHYLSULFONYLPHENYL)THIOPHENE; ACETYLSALICYLIC ACID; ARACHIDONIC ACID; CELECOXIB; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; CYCLOOXYGENASE 3; DICLOFENAC; DIFLUNISAL; IBUPROFEN; INDOMETACIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 1BETA; INTERLEUKIN 6; MELOXICAM; MINOCYCLINE; N (2 CYCLOHEXYLOXY 4 NITROPHENYL)METHANESULFONAMIDE; NAPROXEN; NIMESULIDE; NONSTEROID ANTIINFLAMMATORY AGENT; PLACEBO; PROSTAGLANDIN E2; PROSTAGLANDIN G2; PROSTAGLANDIN H2; PROSTAGLANDIN SYNTHASE; ROFECOXIB; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG; VALDECOXIB;

ALZHEIMER DISEASE; ANALGESIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTIPYRETIC ACTIVITY; CLINICAL TRIAL; CYTOKINE PRODUCTION; DIGESTIVE SYSTEM ULCER; DRUG EFFICACY; DRUG SAFETY; DRUG SELECTIVITY; DRUG STRUCTURE; ENZYME INHIBITION; GASTROINTESTINAL HEMORRHAGE; GASTROINTESTINAL SYMPTOM; HUMAN; IC 50; INFLAMMATION; NONHUMAN; PARKINSON DISEASE; PRIMARY PREVENTION; PROTEIN EXPRESSION; REVIEW; RISK REDUCTION;

EID: 77954938809     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph3061812     Document Type: Review

References (195)

1. Centers for Disease Control and Prevention. Health, United States; National Center for Health Statistics: Hyattsville, MD, USA, 2010.
2. Alzheimer's Association. Alzheimer's disease Facts and Figures, 2010. Alzheimer's Dementia, 2010, 6, 158-194.
3. Levine, D.B.; Fahrbach, K.R.; Siderowf, A.D.; Estok, R.P.; Ludensky, V.M.; Ross, S.D. Diagnosis and Treatment of Parkinson's Disease: A Systematic Review of the Literature; Agency for Healthcare Research and Quality: Rockville, MD, USA, 2003.
4. McGeer, P.L.; Schulzer, M.; McGeer, E.G. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: A review of 17 epidemiologic studies. Neurology 1996, 47, 425-432.
5. Punchard, N.A.; Whelan, C.J.; Adcock, I. The Journal of Inflammation. J. Inflamm. 2004, 1, 1.
6. Vane, J.R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat. New. Biol. 1971, 231, 232-235.
7. Kiefer, J.R.; Pawlitz, J.L.; Moreland, K.T.; Stegeman, R.A.; Hood, W.F.; Gierse, J.K.; Stevens, A.M.; Goodwin, D.C.; Rowlinson, S.W.; Marnett, L.J.; Stallings, W.C.; Kurumbail, R.G. Structural insights into the stereochemistry of the cyclooxygenase reaction. Nature 2000, 405, 97-101.
8. Hein, A.M.; O'Banion, M.K. Neuroinflammation and memory: The role of prostaglandins. Mol. Neurobio. 2009, 40, 15-32.
9. Flower, R.J. The development of COX2 inhibitors. Nat. Rev. Drug Discov. 2003, 2, 179-191.
10. Chandrasekharan, N.V.; Dai, H.; Roos, K.L.T.; Evanson, N.K.; Tomsik, J.; Elton, T.S.; Simmons, D.L. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: Cloning, structure, and expression. Proc. Nat. Acad. Sci. USA 2002, 99, 13926-13931.
11. Kis, B.; Snipes, J.A.; Gaspar, T.; Lenzser, G.; Tulbert, C.D.; Busija, D.W. Cloning of cyclooxygenase-1b (putative COX-3) in mouse. Inflamm. Res. 2006, 55, 274-278.
12. McGeer, P.L. Cyclo-oxygenase-2 inhibitors: Rationale and therapeutic potential for Alzheimer's disease. Drugs Aging 2000, 17, 1-11.
13. Breder, C.D.; Dewitt, D.; Kraig, R.P. Characterization of inducible cyclooxygenase in rat-brain. J. Comp. Neurol. 1995, 355, 296-315.
14. Kaufmann, W.E.; Worley, P.F.; 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. Nat. Acad. Sci. USA 1996, 93, 2317-2321.
15. Yamagata, K.; Andreasson, K.I.; Kaufmann, W.E.; Barnes, C.A.; Worley, P.F. Expression of a mitogen-inducible cyclooxygenase in brain neurons: Regulation by synaptic activity and glucocorticoids. Neuron 1993, 11, 371-386.
16. Hein, A.M.; Stasko, M.R.; Matousek, S.B.; Scott-McKean, J.J.; Maier, S.F.; Olschowka, J.A.; Costa, A.C.S.; O'Banion, M.K. Sustained hippocampal IL-1β overexpression impairs contextual and spatial memory in transgenic mice. Brain Behav. Immun. 2009, 24, 243-253.
17. Moore, A.H.; Olschowka, J.A.; Williams, J.P.; Okunieff, P.; O'Banion, M.K. Regulation of prostaglandin E2 synthesis after brain irradiation. Int. J. Radiat. Oncol. Biol. Phys. 2005, 62, 267-272.
18. Berg, J.M.; Tymoczko, J.L.; Stryer, L. Biochemistry, 6th ed.; Freeman and Company: New York, NY, USA, 2006.
19. Marnett, L.J.; Rowlinson, S.W.; Goodwin, D.C.; Kalgutkar, A.S.; Lanzo, C.A. Arachidonic acid oxygenation by COX-1 and COX-2. Mechanisms of catalysis and inhibition. J. Biol. Chem. 1999, 274, 22903-22906.
20. Cleland, L. G.; James, M. J. COX-2 selectivity varies across class. Med. J. Aust. 2005, 182, 197-198.
21. Vane, J.R.; Botting, R.M. Anti-inflammatory drugs and their mechanism of action. Inflamm. Res. 1998, 47 (Suppl. 2), S78-S87.
22. Graeber, M.B.; Streit, W.J. Microglia: Biology and pathology. Acta Neuropathol. 2010, 119, 89-105.
23. Griffin, W.S.T.; Sheng, J.G.; Royston, M.C.; Gentleman, S.M.; McKenzie, J.E.; Graham, D.I.; Roberts, G.W.; Mrak, R.E. Glial-neuronal interactions in Alzheimer's disease: The potential role of a ''cytokine cycle'' in disease progression. Brain Pathol. 1998, 8, 65-72.
24. Cacquevel, M.; Lebeurrier, N.; Cheenne, S.; Vivien, D. Cytokines in neuroinflammation and Alzheimer's disease. Curr. Drug Targets 2004, 5, 529-534.
25. Shaftel, S.S.; Griffin, W.S.T.; O'Banion, M.K. The role of interleukin-1 in neuroinflammation and Alzheimer disease: An evolving perspective. J. Neuroinflamm. 2008, 5, 12.
26. Cimino, P.J.; Keene, C.D.; Breyer, R.M.; Montine, K.S.; Montine, T.J. Therapeutic targets in prostaglandin E-2 signaling for neurologic disease. Curr. Med. Chem. 2008, 15, 1863-1869.
27. Chen, C.; Bazan, N.G. Endogenous PGE(2) regulates membrane excitability and synaptic transmission in hippocampal CA1 pyramidal neurons. J. Neurophysiol. 2005, 93, 929-941.
28. Chen, C.; Magee, J.C.; Bazan, N.G. Cyclooxygenase-2 regulates prostaglandin E-2 signaling in hippocampal long-term synaptic plasticity. J. Neurophysiol. 2002, 87, 2851-2857.
29. Le, T.D.; Shirai, Y.; Okamoto, T.; Tatsukawa, T.; Nagao, S.; Shimizu, T.; Ito, M. Lipid signaling in cytosolic phospholipase A(2)alpha-cyclooxygenase-2 cascade mediates cerebellar long-term depression and motor learning. Proc. Nat. Acad. Sci. USA 2010, 107, 3198-3203.
30. Savonenko, A.; Munoz, P.; Melnikova, T.; Wang, Q.; Liang, X.; Breyer, R.M.; Montine, T.J.; Kirkwood, A.; Andreasson, K. Impaired cognition, sensorimotor gating, and hippocampal long-term depression in mice lacking the prostaglandin E2 EP2 receptor. Exp. Neurol. 2009, 217, 63-73.
31. Shie, F.S.; Montine, K.S.; Breyer, R.M.; Montine, T.J. Microglial EP2 is critical to neurotoxicity from activated cerebral innate immunity. Glia 2005, 52, 70-77.
32. Takemiya, T.; Maehara, M.; Matsumura, K.; Yasuda, S.; Sugiura, H.; Yamagata, K. Prostaglandin E-2 produced by late induced COX-2 stimulates hippocampal neuron loss after seizure in the CA3 region. Neurosci. Res. 2006, 56, 103-110.
33. Brown, G.C.; Bal-Price, A. Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria. Mol. Neurobiol. 2003, 27, 325-355.
34. Calabrese, V.; Bates, T.E.; Stella, A.M.G. NO synthase and NO-dependent signal pathways in brain aging and neurodegenerative disorders: The role of oxidant/antioxidant balance. Neurochem. Res. 2000, 25, 1315-1341.
35. Dawson, V.L.; Dawson, T.M. Nitric oxide in neurodegeneration. Prog. Brain Res. 1998, 118, 215-229.
36. Parepally, J.M.R.; Mandula, H.; Smith, Q.R. Brain uptake of nonsteroidal anti-inflammatory drugs: Ibuprofen, flurbiprofen, and indomethacin. Pharmaceut. Res. 2006, 23, 873-881.
37. Plassman, B.L.; Langa, K.M.; Fisher, G.G.; Heeringa, S.G.; Weir, D.R.; Ofstedal, M.B.; Burke, J.R.; Hurd, M.D.; Potter, G.G.; Rodgers, W.L.; Steffens, D.C.; Willis, R.J.; Wallace, R.B. Prevalence of dementia in the united states: The aging, demographics, and memory study. Neuroepidemiology 2007, 29, 125-132.
38. World Health Organization. Neurological Disorders: Public health challenges; http://www.who.int/mental_health/neurology/neurodiso/en/index.html (accessed June 01, 2010).
39. Wimo, A.; Winblad, B.; Jonsson, L. An estimate of the total worldwide societal costs of dementia in 2005. Alzheimer. Dement. 2007, 3, 81-91.
40. Akiyama, H.; Barger, S.; Barnum, S.; Bradt, B.; Bauer, J.; Cole, G.M.; Cooper, N.R.; Eikelenboom, P.; Emmerling, M.; Fiebich, B.L.; Finch, C.E.; Frautschy, S.; Griffin, W.S.; Hampel, H.; Hull, M.; Landreth, G.; Lue, L.; Mrak, R.; Mackenzie, I.R.; McGeer, P.L.; O'Banion, M.K.; Pachter, J.; Pasinetti, G.; Plata-Salaman, C.; Rogers, J.; Rydel, R.; Shen, Y.; Streit, W.; Strohmeyer, R.; Tooyoma, I.; Van Muiswinkel, F.L.; Veerhuis, R.; Walker, D.; Webster, S.; Wegrzyniak, B.; Wenk, G.; Wyss-Coray, T. Inflammation and Alzheimer's disease. Neurobiol. Aging 2000, 21, 383-421.
41. Cagnin, A.; Brooks, D.J.; Kennedy, A.M.; Gunn, R.N.; Myers, R.; Turkheimer, F.E.; Jones, T.; Banati, R.B. In vivo measurement of activated microglia in dementia. Lancet 2001, 358, 461-467.
42. Small, G.W.; Agdeppa, E.D.; Kepe, V.; Satyamurthy, N.; Huang, S.C.; Barrio, J.R. In vivo brain imaging of tangle burden in humans. J. Mol. Neurosci. 2002, 19, 323-327.
43. Small, G.W.; Bookheimer, S.Y.; Thompson, P.M.; Cole, G.M.; Huang, S.C.; Kepe, V.; Barrio, J.R. Current and future uses of neuroimaging for cognitively impaired patients. Lancet Neurol. 2008, 7, 161-172.
44. McGeer, P.L.; Itagaki, S.; Tago, H.; McGeer, E.G. 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.
45. Rogers, J.; Lubernarod, J.; Styren, S.D.; Civin, W.H. Expression of immune system-associated antigens by cells of the human central nervous-system: Relationship to the pathology of alzheimers-disease. Neurobiol. Aging 1988, 9, 339-349.
46. Oddo, S.; Caccamo, A.; Shepherd, J.D.; Murphy, M.P.; Golde, T.E.; Kayed, R.; Metherate, R.; Mattson, M.P.; Akbari, Y.; LaFerla, F.M. Triple-transgenic model of Alzheimer's disease with plaques and tangles: Intracellular Abeta and synaptic dysfunction. Neuron 2003, 39, 409-421.
47. Philipson, O.; Lord, A.; Gumucio, A.; O'Callaghan, P.; Lannfelt, L.; Nilsson, L.N.G. Animal models of amyloid-β-related pathologies in Alzheimer's disease. FEBS J. 2010, 277, 1389-1409.
48. Meda, L.; Baron, P.; Scarlato, G. Glial activation in Alzheimer's disease: The role of Abeta and its associated proteins. Neurobiol. Aging 2001, 22, 885-893.
49. Fujimi, K.; Noda, K.; Sasaki, K.; Wakisaka, Y.; Tanizaki, Y.; Iida, M.; Kiyohara, Y.; Kanba, S.; Iwaki, T. Altered expression of COX-2 in infdivisions of the hippocampus during aging and in Alzheimer's disease: The Hisayama study. Dement. Geriatr. Cogn. Disord. 2007, 23, 423-431.
50. Hoozemans, J.J.M.; Rozemuller, J.M.; van Haastert, E.S.; Veerhuis, R.; Eikelenboom, P. Cyclooxygenase-1 and-2 in the different stages of Alzheimer's disease pathology. Curr. Pharm. Design 2008, 14, 1419-1427.
51. Yermakova, A.V.; O'Banion, M.K. Downregulation of neuronal cyclooxygenase-2 expression in end stage Alzheimer's disease. Neurobiol. Aging 2001, 22, 823-836.
52. Conde, J.R.; Streit, W.J. Microglia in the aging brain. J. Neuropathol. Exp. Neurol. 2006, 65, 199-203.
53. Griffin, R.; Nally, R.; Nolan, Y.; McCartney, Y.; Linden, J.; Lynch, M.A. The age-related attenuation in long-term potentiation is associated with microglial activation. J. Neurochem. 2006, 99, 1263-1272.
54. Murray, C.A.; Lynch, M.A. Evidence that increased hippocampal expression of the cytokine interleukin-1β is a common trigger for age- and stress-induced impairments in long-term potentiation. J. Neurosci. 1998, 18, 2974-2981.
55. Perry, V.H.; Matyszak, M.K.; Fearn, S. Altered antigen expression of microglia in the aged rodent CNS. Glia 1993, 7, 60-67.
56. Sheffield, L.G.; Berman, N.E.J. Microglial expression of MHC class II increases in normal aging of nonhuman primates. Neurobiol. Aging 1998, 19, 47-55.
57. Hauss-Wegrzyniak, B.; Dobrzanski, P.; Stoehr, J.D.; Wenk, G.L. Chronic neuroinflammation in rats reproduces components of the neurobiology of Alzheimer's disease. Brain Res. 1998, 780, 294-303.
58. Hauss-Wegrzyniak, B.; Galons, J.P.; Wenk, G.L. Quantitative volumetric analyses of brain magnetic resonance imaging from rat with chronic neuroinflammation. Exp. Neurol. 2000, 165, 347-354.
59. Moore, A.H.; Wu, M.; Shaftel, S.S.; Graham, K.A.; O'Banion, M.K. Sustained expression of interleukin-1β in mouse hippocampus impairs spatial memory. Neuroscience 2009, 164, 1484-1495.
60. Yoshiyama, Y.; Higuchi, M.; Zhang, B.; Huang, S.M.; Iwata, N.; Saido, T.C.; Maeda, J.; Suhara, T.; Trojanowski, J.Q.; Lee, V.M. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 2007, 53, 337-351.
61. Kitazawa, M.; Oddo, S.; Yamasaki, T.R.; Green, K.N.; LaFerla, F.M. Lipopolysaccharideinduced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer's disease. J. Neurosci. 2005, 25, 8843-8853.
62. Li, Y.; Liu, L.; Barger, S.W.; Griffin, W.S. Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway. J. Neurosci. 2003, 23, 1605-1611.
63. Andreasson, K.I.; Savonenko, A.; Vidensky, S.; Goellner, J.J.; Zhang, Y.; Shaffer, A.; Kaufmann, W.E.; Worley, P.F.; Isakson, P.; Markowska, A.L. Age-dependent cognitive deficits and neuronal apoptosis in cyclooxygenase-2 transgenic mice. J. Neurosci. 2001, 21, 8198-8209.
64. Hoshino, T.; Nakaya, T.; Homan, T.; Tanaka, K.I.; Sugimoto, Y.; Araki, W.; Narita, M.; Narumiya, S.; Suzuki, T.; Mizushima, T. Involvement of prostaglandin E-2 in production of amyloid-beta peptides both in vitro and in vivo. J. Biol. Chem. 2007, 282, 32676-32688.
65. Liang, X.B.; Wang, Q.; Hand, T.; Wu, L.J.; Breyer, R.M.; Montine, T.J.; Andreasson, K. Deletion of the prostaglandin E-2 EP2 receptor reduces oxidative damage and amyloid burden in a model of Alzheimer's disease. J. Neurosci. 2005, 25, 10180-10187.
66. Imbimbo, B. P. An update on the efficacy of non-steroidal anti-inflammatory drugs in Alzheimer's disease. Expert Opin. Investig. Drugs 2009, 18, 1147-1168.
67. Lim, G.P.; Yang, F.; Chu, T.; Chen, P.; Beech, W.; Teter, B.; Tran, T.; Ubeda, O.; Ashe, K.H.; Frautschy, S.A.; Cole, G.M. Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. J. Neurosci. 2000, 20, 5709-5714.
68. Yan, Q.; Zhang, J.H.; Liu, H.T.; Babu-Khan, S.; Vassar, R.; Biere, A.L.; Citron, M.; Landreth, G. Anti-inflammatory drug therapy alters beta-amyloid processing and deposition in an animal model of Alzheimer's disease. J. Neurosci. 2003, 23, 7504-7509.
69. Stephan, A.; Laroche, S.; Davis, S. Learning deficits and dysfunctional synaptic plasticity induced by aggregated amyloid deposits in the dentate gyrus are rescued by chronic treatment with indomethacin. Eur. J. Neurosci. 2003, 17, 1921-1927.
70. Cakala, M.; Malik, A.R.; Strosznajder, J.B. Inhibitor of cyclooxygenase-2 protects against amyloid beta peptide-evoked memory impairment in mice. Pharmacol. Rep. 2007, 59, 164-172.
71. Rogers, J.; Kirby, L.C.; Hempelman, S.R.; Berry, D.L.; McGeer, P.L.; Kaszniak, A.W.; Zalinski, J.; Cofield, M.; Mansukhani, L.; Willson, P.; et al. Clinical trial of indomethacin in Alzheimer's disease. Neurology 1993, 43, 1609-1611.
72. Aisen, P.S.; Schafer, K.A.; Grundman, M.; Pfeiffer, E.; Sano, M.; Davis, K.L.; Farlow, M.R.; Jin, S.; Thomas, R.G.; Thal, L.J. Effects of rofecoxib or naproxen vs. placebo on Alzheimer disease progression: A randomized controlled trial. JAMA 2003, 289, 2819-2826.
73. de Jong, D.; Jansen, R.; Hoefnagels, W.; Jellesma-Eggenkamp, M.; Verbeek, M.; Borm, G.; Kremer, B. No effect of one-year treatment with indomethacin on Alzheimer's disease progression: A randomized controlled trial. Plos One 2008, 3, e1475
74. Pasqualetti, P.; Bonomini, C.; Dal Forno, G.; Paulon, L.; Sinforiani, E.; Marra, C.; Zanetti, O.; Rossini, P.M. A randomized controlled study on effects of ibuprofen on cognitive progression of Alzheimer's disease. Aging Clin. Exp. Res. 2009, 21, 102-110.
75. Reines, S.A.; Block, G.A.; Morris, J.C.; Liu, G.; Nessly, M.L.; Lines, C.R.; Norman, B.A.; Baranak, C.C. Rofecoxib: No effect on Alzheimer's disease in a 1-year, randomized, blinded, controlled study. Neurology 2004, 62, 66-71.
76. 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.
77. Aisen, P.S.; Schmeidler, J.; Pasinetti, G.M. Randomized pilot study of nimesulide treatment in Alzheimer's disease. Neurology 2002, 58, 1050-1054.
78. Thal, L.J.; Ferris, S.H.; Kirby, L.; Block, G.A.; Lines, C.R.; Yuen, E.; Assaid, C.; Nessly, M.L.; Norman, B.A.; Baranak, C.C.; Reines, S.A. A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment. Neuropsychopharmacology 2005, 30, 1204-1215.
79. McGeer, P.L.; McGeer, E.G. NSAIDs and Alzheimer disease: Epidemiological, animal model and clinical studies. Neurobiol. Aging 2007, 28, 639-647.
80. Townsend, K.P.; Pratico, D. Novel therapeutic opportunities for Alzheimer's disease: Focus on nonsteroidal anti-inflammatory drugs. FASEB J. 2005, 19, 1592-1601.
81. Martin, B.K.; Szekely, C.; Brandt, J.; Piantadosi, S.; Breitner, J.C.S.; Craft, S.; Evans, D.; Green, R.; Mullan, M.; Grp, A.R. Cognitive function over time in the Alzheimer's disease anti-inflammatory prevention trial (ADAPT): Results of a randomized, controlled trial of naproxen and celecoxib. Arch. Neurol. 2008, 65, 896-905.
82. Couzin, J. Clinical trials: Halt of Celebrex study threatens drug's future, other trials. Science 2004, 306, 2170-2170.
83. Shaftel, S.S.; Kyrkanides, S.; Olschowka, J.A.; Miller, J.N.; Johnson, R.E.; O'Banion, M.K. Sustained hippocampal IL-1β overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology. J. Clin. Invest. 2007, 117, 1595-1604.
84. Small, G.W.; Siddarth, P.; Silverman, D.H.; Ercoli, L.M.; Miller, K.J.; Lavretsky, H.; Bookheimer, S.Y.; Huang, S.C.; Barrio, J.R.; Phelps, M.E. Cognitive and cerebral metabolic effects of celecoxib vs. placebo in people with age-related memory loss: Randomized controlled study. Am. J. Geriatr. Psychiatry 2008, 16, 999-1009.
85. Mosconi, L.; Rinne, J.O.; Tsui, W.H.; Berti, V.; Li, Y.; Wang, H.; Murray, J.; Scheinin, N.; Nagren, K.; Williams, S.; Glodzik, L.; De Santi, S.; Vallabhajosula, S.; de Leon, M.J. Increased fibrillar amyloid-β burden in normal individuals with a family history of late-onset Alzheimer's. Proc. Natl. Acad. Sci. USA 2010, 107, 5949-5954.
86. Yang, H.W.; Zhang, J.; Breyer, R.M.; Chen, C. Altered hippocampal long-term synaptic plasticity in mice deficient in the PGE2 EP2 receptor. J. Neurochem. 2009, 108, 295-304.
87. Cowley, T.R.; Fahey, B.; O'Mara, S.M. 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, 27, 2999-3008.
88. Guzman, C.B.; Graham, K.A.; Grace, L.A.; Moore, A.H. Sex-dependent effect of cyclooxygenase-2 inhibition on mouse spatial memory. Behav. Brain Res. 2009, 199, 355-359.
89. Rall, J.M.; Mach, S.A.; Dash, P.K. Intrahippocampal infusion of a cyclooxygenase-2 inhibitor attenuates memory acquisition in rats. Brain Res. 2003, 968, 273-276.
90. Sharifzadeh, M.; Naghdi, N.; Khosrovani, S.; Ostad, S.N.; Sharifzadeh, K.; Roghani, A. Posttraining intrahippocampal infusion of the COX-2 inhibitor celecoxib impaired spatial memory retention in rats. Eur. J. Pharmacol. 2005, 511, 159-166.
91. Teather, L.A.; Packard, M.G.; Bazan, N.G. Post-training cyclooxygenase-2 (COX-2) inhibition impairs memory consolidation. Learn. Memory 2002, 9, 41-47.
92. Choi, S.H.; Aid, S.; Bosetti, F. The distinct roles of cyclooxygenase-1 and -2 in neuroinflammation: Implications for translational research. Trends Pharmacol. Sci. 2009, 30, 174-181.
93. Szekely, C.A.; Green, R.C.; Breitner, J.C.S.; Ostbye, T.; Beiser, A.S.; Corrada, M.M.; Dodge, H.H.; Ganguli, M.; Kawas, C.H.; Kuller, L.H.; Psaty, B.M.; Resnick, S.M.; Wolf, P.A.; Zonderman, A.B.; Welsh-Bohmer, K.A.; Zandi, P.P. No advantage of Aβ42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology 2008, 70, 2291-2298.
94. Vlad, S.C.; Miller, D.R.; Kowall, N.W.; Felson, D.T. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 2008, 70, 1672-1677.
95. Waldstein, S.R.; Wendell, C.R.; Seliger, S.L.; Ferrucci, L.; Metter, E.J.; Zonderman, A.B. Nonsteroidal anti-inflammatory drugs, Aspirin, and cognitive function in the Baltimore longitudinal study of aging. J. Amer. Geriat. Soc. 2010, 58, 38-43.
96. Choi, Y.; Kim, H.S.; Shin, K.Y.; Kim, E.M.; Kim, M.; Park, C.H.; Jeong, Y.H.; Yoo, J.; Lee, J.P.; Chang, K.A.; Kim, S.; Suh, Y.H. Minocycline attenuates neuronal cell death and improves cognitive impairment in Alzheimer's disease models. Neuropsychopharmacology 2007, 32, 2393-2404.
97. Noble, W.; Garwood, C.; Stephenson, J.; Kinsey, A.M.; Hanger, D.P.; Anderton, B.H. Minocycline reduces the development of abnormal tau species in models of Alzheimer's disease. FASEB J. 2009, 23, 739-750.
98. Breitner, J.C.; Haneuse, S.J.; Walker, R.; Dublin, S.; Crane, P.K.; Gray, S.L.; Larson, E.B. Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort. Neurology 2009, 72, 1899-1905.
99. McKeage, K.; Blick, S.K.A.; Croxtall, J.D.; Lyseng-Williamson, K.A.; Keating, G.M. Esomeprazole: A review of its use in the management of gastric acid-related diseases in adults. Drugs 2008, 68, 1571-1607.
100. Lleo, A.; Galea, E.; Sastre, M. Molecular targets of non-steroidal anti-inflammatory drugs in neurodegenerative diseases. Cell. Mol. Life Sci. 2007, 64, 1403-1418.
101. Meinert, C.L.; McCaffrey, L.D.; Breitner, J.C. Alzheimer's disease anti-inflammatory prevention trial: Design, methods, and baseline results. Alzheimers Dement. 2009, 5, 93-104.
102. Beher, D.; Clarke, E.E.; Wrigley, J.D.J.; Martin, A.C.L.; Nadin, A.; Churcher, I.; Shearman, M.S. Selected non-steroidal anti-inflammatory drugs and their derivatives target gammasecretase at a novel site: Evidence for an allosteric mechanism. J. Biol. Chem. 2004, 279, 43419-43426.
103. Heneka, M.T.; Sastre, M.; Dumitrescu-Ozimek, L.; Hanke, A.; Dewachter, I.; Kuiperi, C.; O'Banion, K.; Klockgether, T.; Van Leuven, F.; Landreth, G.E. Acute treatment with the PPARγ agonist pioglitazone and ibuprofen reduces glial inflammation and Aβ1-42 levels in APPV717I transgenic mice. Brain 2005, 128, 1442-1453.
104. Jantzen, P.T.; Connor, K.E.; DiCarlo, G.; Wenk, G.L.; Wallace, J.L.; Rojiani, A.M.; Coppola, D.; Morgan, D.; Gordon, M.N. Microglial activation and β-amyloid deposit reduction caused by a nitric oxide-releasing nonsteroidal anti-inflammatory drug in amyloid precursor protein plus presenilin-1 transgenic mice. J. Neurosci. 2002, 22, 2246-2254.
105. Morihara, T.; Chu, T.; Ubeda, O.; Beech, W.; Cole, G.M. Selective inhibition of Aβ42 production by NSAID R-enantiomers. J. Neurochem. 2002, 83, 1009-1012.
106. Weggen, S.; Eriksen, J.L.; Das, P.; Sagi, S.A.; Wang, R.; Pietrzik, C.U.; Findlay, K.A.; Smith, T.E.; Murphy, M.P.; Butler, T.; Kang, D.E.; Marquez-Sterling, N.; Golde, T.E.; Koo, E.H. A infset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity. Nature 2001, 414, 212-216.
107. Green, R.C.; Schneider, L.S.; Amato, D.A.; Beelen, A.P.; Wilcock, G.; Swabb, E.A.; Zavitz, K.H. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: A randomized controlled trial. JAMA 2009, 302, 2557-2564.
108. Masters, C. Anti-inflammatory drugs fall short in Alzheimer's disease. Nature Med. 2008, 14, 916.
109. Hayden, K.M.; Zandi, P.P.; Khachaturian, A.S.; Szekely, C.A.; Fotuhi, M.; Norton, M.C.; Tschanz, J.T.; Pieper, C.F.; Corcoran, C.; Lyketsos, C.G.; Breitner, J.C.; Welsh-Bohmer, K.A. Does NSAID use modify cognitive trajectories in the elderly? The Cache County study. Neurology 2007, 69, 275-282.
110. Szekely, C.A.; Breitner, J.C.; Fitzpatrick, A.L.; Rea, T.D.; Psaty, B.M.; Kuller, L.H.; Zandi, P.P. NSAID use and dementia risk in the Cardiovascular Health Study: Role of APOE and NSAID type. Neurology 2008, 70, 17-24.
111. Kim, J.; Basak, J.M.; Holtzman, D.M. The role of apolipoprotein E in Alzheimer's disease. Neuron 2009, 63, 287-303.
112. Calabresi, P.; Picconi, B.; Parnetti, L.; Di Filippo, M. A convergent model for cognitive dysfunctions in Parkinson's disease: The critical dopamine-acetylcholine synaptic balance. Lancet Neurol. 2006, 5, 974-983.
113. Lang, A.E.; Lozano, A.M. Parkinson's disease: First of two parts. N. Engl. J. Med. 1998, 339, 1044-1053.
114. Double, K.L.; Dedov, V.N.; Fedorow, H.; Kettle, E.; Halliday, G.M.; Garner, B.; Brunk, U.T. The comparative biology of neuromelanin and lipofuscin in the human brain. Cell. Mol. Life Sci. 2008, 65, 1669-1682.
115. Fasano, M.; Giraudo, S.; Coha, S.; Bergamasco, B.; Lopiano, L. Residual infstantia nigra neuromelanin in Parkinson's disease is cross-linked to α;-synuclein. Neurochem. Int. 2003, 42, 603-606.
116. Lang, A.E.; Lozano, A.M. Parkinson's disease: Second of two parts. N. Engl. J. Med. 1998, 339, 1130-1143.
117. nd, 2010).
118. McGeer, P.L.; Itagaki, S.; Boyes, B.E.; McGeer, E.G. Reactive microglia are positive for HLA-DR in the infstantia nigra of parkinsons and alzheimers-disease brains. Neurology 1988, 38, 1285-1291.
119. Langston, J.W.; Forno, L.S.; Tetrud, J.; Reeves, A.G.; Kaplan, J.A.; Karluk, D. Evidence of active nerve cell degeneration in the infstantia nigra of humans years after 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine exposure. Ann. Neurol. 1999, 46, 598-605.
120. Tansey, M.G.; Goldberg, M.S. Neuroinflammation in Parkinson's disease: Its role in neuronal death and implications for therapeutic intervention. Neurobiol. Dis. 2010, 37, 510-518.
121. Wilms, H.; Zecca, L.; Rosenstiel, P.; Sievers, J.; Deuschl, G.; Lucius, R. Inflammation in Parkinson's diseases and other neurodegenerative diseases: Cause and therapeutic implications. Curr. Pharm. Design 2007, 13, 1925-1928.
122. Araujo, D.M.; Lapchak, P.A. Induction of immune-system mediators in the hippocampal- formation in alzheimers and parkinsons diseases: Selective effects on specific interleukins and interleukin receptors. Neuroscience 1994, 61, 745-754.
123. Hunot, S.; Dugas, N.; Dugas, B.; Michel, P.P.; Faucheux, B.; Agid, Y.; Hirsch, E.C. Inflammatory mediators are expressed in the infstantia nigra of patients with Parkinson's disease. Eur. J. Neurosci. 1998, 10, 6919.
124. Mogi, M.; Harada, M.; Kondo, T.; Riederer, P.; Inagaki, H.; Minami, M.; Nagatsu, T. Interleukin-1-β, interleukin-6, epidermal growth-factor and transforming growth-factor-α; are elevated in the brain from parkinsonian-patients. Neurosci. Lett. 1994, 180, 147-150.
125. Mogi, M.; Harada, M.; Riederer, P.; Narabayashi, H.; Fujita, K.; Nagatsu, T. tumor-necrosisfactor-α; (TNF-α;) increases both in the brain and in the cerebrospinal-fluid from parkinsonianpatients. Neurosci. Lett. 1994, 165, 208-210.
126. Wilms, H.; Rosenstiel, P.; Sievers, J.; Deuschl, G.; Zecca, L.; Lucius, R. Activation of microglia by human neuromelanin is NF-κB dependent and involves p38 mitogen-activated protein kinase: implications for Parkinson's disease. FASEB J. 2003, 17, 500-502.
127. Gerhard, A.; Pavese, N.; Hotton, G.; Turkheimer, F.; Es, M.; Hammers, A.; Eggert, K.; Oertel, W.; Banati, R.B.; Brooks, D.J. In vivo imaging of microglial activation with C-11 (R)-PK11195 PET in idiopathic Parkinson's disease. Neurobiol. Dis. 2006, 21, 404-412.
128. Ouchi, Y.; Yoshikawa, E.; Sekine, Y.; Futatinfashi, M.; Kanno, T.; Ogusu, T.; Torizuka, T. Microglial activation and dopamine terminal loss in early Parkinson's disease. Ann. Neurol. 2005, 57, 168-175.
129. Kim, W.G.; Mohney, R.P.; Wilson, B.; Jeohn, G.H.; Liu, B.; Hong, J.S. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: Role of microglia. J. Neurosci. 2000, 20, 6309-6316.
130. Lima, M.D.S.; Reksidler, A.B.; Zanata, S.M.; Machado, H.B.; Tufik, S.; Vital, M. Different parkinsonism models produce a time-dependent induction of COX-2 in the infstantia nigra of rats. Brain Res. 2006, 1101, 117-125.
131. Kanaan, N.M.; Kordower, J.H.; Collier, T.J. Age-related changes in glial cells of dopamine midbrain infregions in rhesus monkeys. Neurobiol. Aging 2008, 31, 937-952.
132. Wang, T.G.; Pei, Z.; Zhang, W.; Liu, B.; Langenbach, R.; Lee, C.; Wilson, B.; Reece, J.M.; Miller, D.S.; Hong, J.S. MPP+-induced COX-2 activation and infsequent dopaminergic neurodegeneration. FASEB J. 2005, 19, 1134-1136.
133. Teismann, P.; Tieu, K.; Choi, D.K.; Wu, D.C.; Naini, A.; Hunot, S.; Vila, M.; Jackson-Lewis, V.; Przedborski, S. Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration. Proc. Nat. Acad. Sci. USA 2003, 100, 5473-5478.
134. Feng, Z.H.; Wang, T.G.; Li, D.D.; Fung, P.; Wilson, B.C.; Liu, B.; Ali, S.F.; Langenbach, R.; Hong, J.S. Cyclooxygenase-2-deficient mice are resistant to 1-methyl-4-phenyl1,2,3,6- tetrahydropyridine-induced damage of dopaminergic neurons in the infstantia nigra. Neurosci. Lett. 2002, 329, 354-358.
135. Carrasco, E.; Casper, D.; Werner, P. Dopaminergic neurotoxicity by 6-OHDA and MPP+: Differential requirement for neuronal cyclooxygenase activity. J. Neurosci. Res. 2005, 81, 121-131.
136. Carrasco, E.; Casper, D.; Werner, P. PGE(2) receptor EP1 renders dopaminergic neurons selectively vulnerable to low-level oxidative stress and direct PGE(2) neurotoxicity. J. Neurosci. Res. 2007, 85, 3109-3117.
137. Carrasco, E.; Werner, P.; Casper, D. Prostaglandin receptor EP2 protects dopaminergic neurons against 6-OHDA-mediated low oxidative stress. Neurosci. Lett. 2008, 441, 44-49.
138. Shie, F.S.; Montine, K.S.; Breyer, R.M.; Montine, T.J. Microglial EP2 is critical to neurotoxicity from activated cerebral innate immunity. Glia 2005, 52, 70-77.
139. Jin, J.J.; Shie, F.S.; Liu, J.; Wang, Y.; Davis, J.; Schantz, A.M.; Montine, K.S.; Montine, T.J.; Zhang, J. Prostaglandin E-2 receptor inftype 2 (EP2) regulates microglial activation and associated neurotoxicity induced by aggregated α;-synuclein. J. Neuroinflamm. 2007, 4, 10.
140. Przedborski, S.; Goldman, J.E. Pathogenic role of glial cells in Parkinson's disease. Advan. Mol. Cell Biol. 2004, 31, 967-982.
141. Hirsch, E.C.; Hunot, S. Neuroinflammation in Parkinson's disease: A target for neuroprotection? Lancet Neurol. 2009, 8, 382-397.
142. Esposito, E.; Di Matteo, V.; Benigno, A.; Pierucci, M.; Crescimanno, G.; Di Giovanni, G. Non-steroidal anti-inflammatory drugs in Parkinson's disease. Exp. Neurol. 2007, 205, 295-312.
143. Aubin, N.; Curet, O.; Deffois, A.; Carter, C. Aspirin and salicylate protect against MPTP-induced dopamine depletion in mice. J. Neurochem. 1998, 71, 1635-1642.
144. Di Matteo, V.; Pierucci, M.; Di Giovanni, G.; Di Santo, A.; Poggi, A.; Benigno, A.; Esposito, E. Aspirin protects striatal dopaminergic neurons from neurotoxin-induced degeneration: An in vivo microdialysis study. Brain Res. 2006, 1095, 167-177.
145. Maharaj, H.; Maharaj, D.S.; Daya, S. Acetylsalicylic acid and acetaminophen protect against MPP+-induced mitochondrial damage and superoxide anion generation. Life Sci. 2006, 78, 2438-2443.
146. Sairam, K.; Saravanan, K.S.; Banerjee, R.; Mohanakumar, K.P. Non-steroidal anti-inflammatory drug sodium salicylate, but not diclofenac or celecoxib, protects against 1-methyl-4-phenyl pyridinium-induced dopaminergic neurotoxicity in rats. Brain Res. 2003, 966, 245-252.
147. 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, 167-174.
148. Kurkowska-Jastrzebska, I.; Babiuch, M.; Joniec, I.; Przybylkowski, A.; Czlonkowski, A.; Czlonkowska, A. Indomethacin protects against neurodegeneration caused by MPTP intoxication in mice. Int. Immunopharmacol. 2002, 2, 1213-1218.
149. Gupta, A.; Dhir, A.; Kumar, A.; Kulkarni, S.K. Protective effect of cyclooxygenase (COX)- inhibitors against drug-induced catatonia and MPTP-induced striatal lesions in rats. Pharmacol. Biochem. Behav. 2009, 94, 219-226.
150. Klivenyi, P.; Gardian, G.; Calingasan, N.Y.; Yang, L.; Beal, M.F. Additive neuroprotective effects of creatine and a cyclooxygenase 2 inhibitor against dopamine depletion in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. J. Mol. Neurosci. 2003, 21, 191-198.
151. Przybylkowski, A.; Kurkowska-Jastrzebska, I.; Joniec, I.; Ciesielska, A.; Czlonkowska, A.; Czlonkowski, A. Cyclooxygenases mRNA and protein expression in striata in the experimental mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration to mouse. Brain Res. 2004, 1019, 144-151.
152. Reksidler, A.B.; Lima, M.M.S.; Zanata, S.M.; Machado, H.B.; da Cunha, C.; Andreatini, R.; Tufik, S.; Vital, M. The COX-2 inhibitor parecoxib produces neuroprotective effects in MPTPlesioned rats. Eur. J. Pharmacol. 2007, 560, 163-175.
153. Sanchez-Pernaute, R.; Ferree, A.; Cooper, O.; Yu, M.; Brownell, A.L.; Isacson, O. Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease. J. Neuroinflamm. 2004, 1, 6.
154. Chen, H.; Zhang, S.M.; Hernan, M.A.; Schwarzschild, M.A.; Willett, W.C.; Colditz, G.A.; Speizer, F.E.; Ascherio, A. Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch. Neurol. 2003, 60, 1059-1064.
155. Chen, H.L.; Jacobs, E.; Schwarzschild, M.A.; McCullough, M.L.; Calle, E.E.; Thun, M.J.; Ascherio, A. Nonsteroidal antiinflammatory drug use and the risk for Parkinson's disease. Ann. Neurol. 2005, 58, 963-967.
156. Powers, K.M.; Kay, D.M.; Factor, S.A.; Zabetian, C.P.; Higgins, D.S.; Samii, A.; Nutt, J.G.; Griffith, A.; Leis, B.; Roberts, J.W.; Martinez, E.D.; Montimurro, J.S.; Checkoway, H.; Payami, H. Combined effects of smoking, coffee, and NSAIDs on Parkinson's disease risk. Movement Disord. 2008, 23, 88-95.
157. Wahner, A.D.; Bronstein, J.M.; Bordelon, Y.M.; Ritz, B. Nonsteroidal anti-inflammatory drugs may protect against Parkinson disease. Neurology 2007, 69, 1836-1842.
158. Bornebroek, M.; de Lau, L.M.L.; Haag, M.D.M.; Koudstaal, P.J.; Hofman, A.; Stricker, B.H.C.; Breteler, M.M.B. Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Neuroepidemiology 2007, 28, 193-196.
159. Bower, J.H.; Maraganore, D.M.; Peterson, B.J.; Ahlskog, J.E.; Rocca, W.A. Immunologic diseases, anti-inflammatory drugs, and Parkinson disease: A case-control study. Neurology 2006, 67, 494-496.
160. Etminan, M.; Carleton, B.C.; Samii, A. Non-steroidal anti-inflammatory drug use and the risk of Parkinson disease: A retrospective cohort study. J. Clin. Neurosci. 2008, 15, 576-577.
161. Etminan, M.; Suissa, S. NSAID use and the risk of Parkinson's disease. Curr. Drug Saf. 2006, 1, 223-225.
162. Hernan, M.A.; Logroscino, G.; Garcia Rodriguez, L.A. Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease. Neurology 2006, 66, 1097-1099.
163. Gagne, J.J.; Power, M.C. Anti-inflammatory drugs and risk of Parkinson disease: A metaanalysis. Neurology 2010, 74, 995-1002.
164. Samii, A.; Etminan, M.; Wiens, M.O.; Jafari, S. NSAID use and the risk of Parkinson's disease systematic review and meta-analysis of observational studies. Drug. Aging 2009, 26, 769-779.
165. Gao, X.; Chen, H.; Schwarzschild, M.A.; Ascherio, A. Use of the non-steroidal anti-inflammatory drugs of Parkinson's disease: A prospective study and meta-analysis. In American Academy of Neurology 2010 Annual Meeting S03.003, Toronto, Ontario, Canada, April 17, 2010.
166. Hirohata, M.; Ono, K.; Morinaga, A.; Yamada, M. Non-steroidal anti-inflammatory drugs have potent anti-fibrillogenic and fibril-destabilizing effects for alpha-synuclein fibrils in vitro. Neuropharmacology 2008, 54, 620-627.
167. O'Hare, E.; Elliott, J.J.; Hobson, P.; Spanswick, D.; Kim, E.M. Behavioural deterioration induced by intrahippocampal NAC61-95 injections and attenuation with ibuprofen. Behav. Brain Res. 2010, 208, 274-277.
168. Kanaan, N.M.; Kordower, J.H.; Collier, T.J. Age and region-specific responses of microglia, but not astrocytes, suggest a role in selective vulnerability of dopamine neurons after 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine exposure in monkeys. Glia 2008, 56, 1199-1214.
169. Ohashi, S.; Mori, A.; Kurihara, N.; Mitsumoto, Y.; Nakai, M. Age-related severity of dopaminergic neurodegeneration to MPTP neurotoxicity causes motor dysfunction in C57BL/6 mice. Neurosci. Lett. 2006, 401, 183-187.
170. White, W.B.; West, C.R.; Borer, J.S.; Gorelick, P.B.; Lavange, L.; Pan, S.X.; Weiner, E.; Verburg, K.M. Risk of cardiovascular events in patients receiving celecoxib: A meta-analysis of randomized clinical trials. Amer. J. Cardiol. 2007, 99, 91-98.
171. Becker, M.C.; Wang, T.H.; Wisniewski, L.; Wolski, K.; Libby, P.; Luscher, T.F.; Borer, J.S.; Mascette, A.M.; Husni, M.E.; Solomon, D.H.; Graham, D.Y.; Yeomans, N.D.; Krum, H.; Ruschitzka, F.; Lincoff, A.M.; Nissen, S.E.; Precision, I. Rationale, design, and governance of Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen Or Naproxen (PRECISION), a cardiovascular end point trial of nonsteroidal antiinflammatory agents in patients with arthritis. Amer. Heart J. 2009, 157, 606-612.
172. Hurley, S.D.; Olschowka, J.A.; O'Banion, M.K. Cyclooxygenase inhibition as a strategy to ameliorate brain injury. J. Neurotrauma 2002, 19, 1-15.
173. Ahmad, M.; Zhang, Y.Q.; Liu, H.; Rose, M.E.; Graham, S.H. Prolonged opportunity for neuroprotection in experimental stroke with selective blockade of cyclooxygenase-2 activity. Brain Res. 2009, 1279, 168-173.
174. Candelario-Jalil, E. Nimesulide as a promising neuroprotectant in brain ischemia: New experimental evidences. Pharmacol. Res. 2008, 57, 266-273.
175. Dore, S.; Otsuka, T.; Mito, T.; Sugo, N.; Hand, T.; Wu, L.; Hurn, P.D.; Traystman, R.J.; Andreasson, K. Neuronal overexpression of cyclooxygenase-2 increases cerebral infarction. Ann. Neurol. 2003, 54, 155-162.
176. Khansari, P.S.; Halliwell, R.F. Evidence for neuroprotection by the fenamate NSAID, mefenamic acid. Neurochem. Int. 2009, 55, 683-688.
177. Ladecola, C.; Niwa, K.; Nogawa, S.; Zhao, X.R.; Nagayama, M.; Araki, E.; Morham, S.; Ross, M.E. Reduced susceptibility to ischemic brain injury and N-methyl-D-aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice. Proc. Nat. Acad. Sci. USA 2001, 98, 1294-1299.
178. Wakita, H.; Tomimoto, H.; Akiguchi, I.; Lin, J.X.; Miyamoto, K.; Oka, N. A cyclooxygenase-2 inhibitor attenuates white matter damage in chronic cerebral ischemia. Neuroreport 1999, 10, 1461-1465.
179. Bramlett, H.M.; Dietrich, W.D. Quantitative structural changes in white and gray matter 1 year following traumatic brain injury in rats. Acta Neuropathol. 2002, 103, 607-614.
180. Dixon, C.E.; Kochanek, P.M.; Yan, H.Q.; Schiding, J.K.; Griffith, R.G.; Baum, E.; Marion, D.W.; DeKosky, S.T. One-year study of spatial memory performance, brain morphology, and cholinergic markers after moderate controlled cortical impact in rats. J. Neurotrauma 1999, 16, 109-122.
181. Maxwell, W.L.; Povlishock, J.T.; Graham, D.I.A mechanistic analysis of nondisruptive axonal injury: A review. J. Neurotrauma 1997, 14, 419-440.
182. Nonaka, M.; Chen, X.H.; Pierce, J.E.S.; Leoni, M.J.; McIntosh, T.K.; Wolf, J.A.; Smith, D.H. Prolonged activation of NF-κB following traumatic brain injury in rats. J. Neurotrauma 1999, 16, 1023-1034.
183. Evans, R.W.; Evans, R.I.; Sharp, M.J. The physician survey on the post-concussion and whiplash syndromes. Headache 1994, 34, 268-274.
184. Ahmad, M.; Rose, M.E.; Vagni, V.; Griffith, R.P.; Dixon, C.E.; Kochanek, P.M.; Hickey, R.W.; Graham, S.H. Genetic disruption of cyclooxygenase-2 does not improve histological or behavioral outcome after traumatic brain injury in mice. J. Neurosci. Res. 2008, 86, 3605-3612.
185. Kelso, M.L.; Scheff, S.W.; Pauly, J.R.; Loftin, C.D. Effects of genetic deficiency of cyclooxygenase-1 or cyclooxygenase-2 on functional and histological outcomes following traumatic brain injury in mice. BMC Neurosci. 2009, 10,108.
186. Cernak, I.; O'Connor, C.; Vink, R. Inhibition of cyclooxygenase 2 by nimesulide improves cognitive outcome more than motor outcome following diffuse traumatic brain injury in rats. Exp. Brain Res. 2002, 147, 193-199.
187. Dash, P.K.; Mach, S.A.; Moore, A.N. Regional expression and role of cyclooxygenase-2 following experimental traumatic brain injury. J. Neurotrauma 2000, 17, 69-81.
188. Kunz, T.; Marklund, N.; Hillered, L.; Oliw, E.H. Cyclooxygenase-2, prostaglandin synthases, and prostaglandin H-2 metabolism in traumatic brain injury in the rat. J. Neurotrauma 2002, 19, 1051-1064.
189. Kelsen, J.; Kjaer, K.; Chen, G.; Pedersen, M.; Rohl, L.; Frokiaer, J.; Nielsen, S.; Nyengaard, J.R.; Ronn, L.C. Parecoxib is neuroprotective in spontaneously hypertensive rats after transient middle cerebral artery occlusion: A divided treatment response? J. Neuroinflamm. 2006, 3, 31.
190. Browne, K.D.; Iwata, A.; Putt, M.E.; Smith, D.H. Chronic ibuprofen administration worsens cognitive outcome following traumatic brain injury in rats. Exp. Neurol. 2006, 201, 301-307.
191. Streit, W.J. Microglial senescence: Does the brain's immune system have an expiration date? Trends Neurosci. 2006, 29, 506-510.
192. Streit, W.J.; Braak, H.; Xue, Q.S.; Bechmann, I. Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer's disease. Acta Neuropathol. 2009, 118, 475-485.
193. Ahmad, A.S.; Zhuang, H.; Echeverria, V.; Dore, S. Stimulation of prostaglandin EP2 receptors prevents NMDA-induced excitotoxicity. J. Neurotrauma 2006, 23, 1895-1903.
194. Echeverria, V.; Clerman, A.; Dore, S. Stimulation of PGE receptors EP2 and EP4 protects cultured neurons against oxidative stress and cell death following β-amyloid exposure. Eur. J. Neurosci. 2005, 22, 2199-2206.
195. Groeger, A.L.; Cipollina, C.; Cole, M.P.; Woodcock, S.R.; Bonacci, G.; Rudolph, T.K.; Rudolph, V.; Freeman, B.A.; Schopfer, F.J. Cyclooxygenase-2 generates anti-inflammatory mediators from Ω-3 fatty acids. Nat. Chem. Biol. 2010, 6, 433-441.