N-Palmitoylethanolamine-Oxazoline as a New Therapeutic Strategy to Control Neuroinflammation: Neuroprotective Effects in Experimental Models of Spinal Cord and Brain Injury

Journal of Neurotrauma

Volumn 34, Issue 18, 2017, Pages 2609-2623

  Impellizzeri, Daniela ^a   Cordaro, Marika ^a   Bruschetta, Giuseppe ^a   Siracusa, Rosalba ^a   Crupi, Rosalia ^a   Esposito, Emanuela ^a   Cuzzocrea, Salvatore ^a,b  

^a UNIVERSITY OF MESSINA   (Italy)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

ALIAmide; central nervous system; cytokines; inflammation; neurotrophic factors

Indexed keywords

AMIDASE; BRAIN DERIVED NEUROTROPHIC FACTOR; CELL ENZYME; CYCLOOXYGENASE 2; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; GLIAL FIBRILLARY ACIDIC PROTEIN; I KAPPA B KINASE ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 1BETA; N ACYLETHANOLAMINE HYDROLYZING ACID AMIDAS; NEUROTROPHIN 3; OXAZOLINE DERIVATIVE; PALMIDROL; SERINE; TRANSCRIPTION FACTOR RELA; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; CYTOKINE; ETHANOLAMINE DERIVATIVE; NERVE GROWTH FACTOR; NEUROPROTECTIVE AGENT; PALMITIC ACID DERIVATIVE;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BEHAVIOR DISORDER; BRAIN INJURY; CELL NUCLEUS; CONTROLLED STUDY; DISEASE CONTROL; DISEASE MODEL; DRUG SYNTHESIS; ENZYME DEGRADATION; EXPERIMENTAL DISEASE; HISTOPATHOLOGY; INTRACELLULAR TRANSPORT; MALE; MOTOR PERFORMANCE; MOUSE; NERVOUS SYSTEM INFLAMMATION; NEUROPROTECTION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN TRANSPORT; SPINAL CORD INJURY; TREATMENT RESPONSE; ANIMAL; DRUG EFFECT; INFLAMMATION; METABOLISM; MOTOR ACTIVITY; TREATMENT OUTCOME;

ANIMALS; BRAIN INJURIES; CYTOKINES; ETHANOLAMINES; GLIAL FIBRILLARY ACIDIC PROTEIN; INFLAMMATION; MALE; MICE; MODELS, ANIMAL; MOTOR ACTIVITY; NERVE GROWTH FACTORS; NEUROPROTECTIVE AGENTS; PALMITIC ACIDS; SPINAL CORD INJURIES; TREATMENT OUTCOME;

EID: 85029229663     PISSN: 08977151     EISSN: 15579042     Source Type: Journal    
DOI: 10.1089/neu.2016.4808     Document Type: Article

References (51)

1. Nencini, P., Sarti, C., Innocenti, R., Pracucci, G., and Inzitari, D. (2003). Acute inflammatory events and ischemic stroke subtypes. Cerebrovasc. Dis. 15, 215-221.
2. Schmidt, O.I., Heyde, C.E., Ertel, W., and Stahel, P.F. (2005). Closed head injury-an inflammatory disease? Brain Res. Brain Res. Rev. 48, 388-399.
3. Madathil, S.K., Nelson, P.T., Saatman, K.E., and Wilfred, B.R. (2011). MicroRNAs in CNS injury: potential roles and therapeutic implications. Bioessays 33, 21-26.
4. Paterniti, I., Impellizzeri, D., Di Paola, R., Navarra, M., Cuzzocrea, S., and Esposito, E. (2013). A new co-ultramicronized composite including palmitoylethanolamide and luteolin to prevent neuroinflammation in spinal cord injury. J. Neuroinflammation 10, 91.
5. Ahmad, A., Crupi, R., Impellizzeri, D., Campolo, M., Marino, A., Esposito, E., and Cuzzocrea, S. (2012). Administration of palmitoylethanolamide (PEA) protects the neurovascular unit and reduces secondary injury after traumatic brain injury in mice. Brain Behav. Immun. 26, 1310-1321.
6. Esposito, E., Cordaro, M., and Cuzzocrea, S. (2014). Roles of fatty acid ethanolamides (FAE) in traumatic and ischemic brain injury. Pharmacol. Res. 86, 26-31.
7. Ahmad, A., Genovese, T., Impellizzeri, D., Crupi, R., Velardi, E., Marino, A., Esposito, E., and Cuzzocrea, S. (2012). Reduction of ischemic brain injury by administration of palmitoylethanolamide after transient middle cerebral artery occlusion in rats. Brain Res. 1477, 45-58.
8. Solorzano, C., Zhu, C., Battista, N., Astarita, G., Lodola, A., Rivara, S., Mor, M., Russo, R., Maccarrone, M., Antonietti, F., Duranti, A., Tontini, A., Cuzzocrea, S., Tarzia, G., and Piomelli, D. (2009). Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation. Proc. Natl. Acad. Sci. U. S. A. 106, 20966-20971.
9. Saturnino, C., Petrosino, S., Ligresti, A., Palladino, C., De Martino, G., Bisogno, T.. and Di Marzo, V. (2010). Synthesis and biological evaluation of new potential inhibitors of N-acylethanolamine hydrolyzing acid amidase. Bioorg. Med. Chem. Lett. 20, 1210-1213.
10. Sasso, O., Moreno-Sanz, G., Martucci, C., Realini, N., Dionisi, M., Mengatto, L., Duranti, A., Tarozzo, G., Tarzia, G., Mor, M., Bertorelli, R., Reggiani, A., and Piomelli, D. (2013). Antinociceptive effects of the N-acylethanolamine acid amidase inhibitor ARN077 in rodent pain models. Pain 154, 350-360.
11. Li, Y., Yang, L., Chen, L., Zhu, C., Huang, R., Zheng, X., Qiu, Y., and Fu, J. (2012). Design and synthesis of potent N-acylethanolaminehydrolyzing acid amidase (NAAA) inhibitor as anti-inflammatory compounds. PLoS One 7, e43023.
12. Siegmund, S.V., Wojtalla, A., Schlosser, M., Zimmer, A., and Singer, M.V. (2013). Fatty acid amide hydrolase but not monoacyl glycerol lipase controls cell death induced by the endocannabinoid 2- arachidonoyl glycerol in hepatic cell populations. Biochem. Biophys. Res. Commun. 437, 48-54.
13. Hoyer, F.F., Khoury, M., Slomka, H., Kebschull, M., Lerner, R., Lutz, B., Schott, H., Lutjohann, D., Wojtalla, A., Becker, A., Zimmer, A., and Nickenig, G. (2014). Inhibition of endocannabinoid-degrading enzyme fatty acid amide hydrolase increases atherosclerotic plaque vulnerability in mice. J. Mol. Cell Cardiol. 66, 126-132.
14. Skaper, S.D., and Facci, L. (2012). Mast cell-glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 367, 3312-3325.
15. Patent application WO 2013121449 A1. Compositions and methods for the modulation of specific amidases for n-acylethanolamines for use in the therapy of inflammatory diseases. August 22, 2013.
16. Impellizzeri, D., Cordaro, M., Bruschetta, G., Crupi, R., Pascali, J., Alfonsi, D., Marcolongo, G., and Cuzzocrea, S. (2016). 2-pentadecyl- 2-oxazoline: identification in coffee, synthesis and activity in a rat model of carrageenan-induced hindpaw inflammation. Pharmacol. Res. 108, 23-30.
17. Rivlin, A.S., and Tator, C.H. (1978). Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surg. Neurol. 10, 38-43.
18. Logan, T.T., Villapol, S., and Symes, A.J. TGF-beta superfamily gene expression and induction of the Runx1 transcription factor in adult neurogenic regions after brain injury. PLoS One 8, e59250.
19. Skaper, S.D., Facci, L., Barbierato, M., Zusso, M., Bruschetta, G., Impellizzeri, D., Cuzzocrea, S., and Giusti, P. (2015). NPalmitoylethanolamine and neuroinflammation: a novel therapeutic strategy of resolution. Mol. Neurobiol. 52, 1034-1042.
20. Campolo, M., Esposito, E., Ahmad, A., Di Paola, R., Paterniti, I., Cordaro, M., Bruschetta, G., Wallace, J.L., and Cuzzocrea, S. (2014). Hydrogen sulfide-releasing cyclooxygenase inhibitor ATB-346 enhances motor function and reduces cortical lesion volume following traumatic brain injury in mice. J. Neuroinflammation 11, 196.
21. Paterniti, I., Impellizzeri, D., Crupi, R., Morabito, R., Campolo, M., Esposito, E., and Cuzzocrea, S. (2013). Molecular evidence for the involvement of PPAR-delta and PPAR-gamma in anti-inflammatory and neuroprotective activities of palmitoylethanolamide after spinal cord trauma. J. Neuroinflammation 10, 20.
22. Pellow, S., Chopin, P., File, S.E., and Briley, M. (1985). Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J. Neurosci. Methods 14, 149-167.
23. Zohar, O., Rubovitch, V., Milman, A., Schreiber, S., and Pick, C.G. Behavioral consequences of minimal traumatic brain injury in mice. Acta. Neurobiol. Exp. (Wars.) 71, 36-45.
24. Basso, D.M., Fisher, L.C., Anderson, A.J., Jakeman, L.B., McTigue, D.M., and Popovich, P.G. (2006). Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains. J. Neurotrauma 23, 635-659.
25. Esposito, E., D, I., G, B., M, C., R, S., E, G., R, C., and S, C. (2016). A new co-micronized composite containing palmitoylethanolamide and polydatin shows superior oral efficacy compared to their association in a rat paw model of carrageenan-induced inflammation. Eur. J. Pharmacol. 782, 107-118.
26. Eng, L.F., and Ghirnikar, R.S. (1994). GFAP and astrogliosis. Brain Pathol. 4, 229-237.
27. Surh, Y.J., Chun, K.S., Cha, H.H., Han, S.S., Keum, Y.S., Park, K.K., and Lee, S.S. (2001). Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: downregulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat. Res. 480-481, 243-268.
28. Buckley, C.D., Gilroy, D.W., Serhan, C.N., Stockinger, B., and Tak, P.P. (2013). The resolution of inflammation. Nat. Rev. Immunol. 13, 59-66.
29. Piomelli, D., and Sasso, O. (2014). Peripheral gating of pain signals by endogenous lipid mediators. Nat. Neurosci. 17, 164-174.
30. Impellizzeri, D., Bruschetta, G., Cordaro, M., Crupi, R., Siracusa, R., Esposito, E., and Cuzzocrea, S. (2014). Micronized/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain. J. Neuroinflammation 11, 136.
31. Alhouayek, M., and Muccioli, G.G. (2014). Harnessing the antiinflammatory potential of palmitoylethanolamide. Drug Discov. Today 19, 1632-1639.
32. Fidaleo, M., Fanelli, F., Ceru, M.P., and Moreno, S. (2014). Neuroprotective properties of peroxisome proliferator-activated receptor alpha (PPARalpha) and its lipid ligands. Curr. Med. Chem. 21, 2803-2821.
33. Mattace Raso, G., Russo, R., Calignano, A., and Meli, R. (2014). Palmitoylethanolamide in CNS health and disease. Pharmacol. Res. 86, 32-41.
34. Ueda, N., Tsuboi, K., and Uyama, T. (2010). N-acylethanolamine metabolism with special reference to N-acylethanolamine-hydrolyzing acid amidase (NAAA). Prog. Lipid Res. 49, 299-315.
35. Yamano, Y., Tsuboi, K., Hozaki, Y., Takahashi, K., Jin, X.H., Ueda, N., and Wada, A. (2012). Lipophilic amines as potent inhibitors of Nacylethanolamine- hydrolyzing acid amidase. Bioorg. Med. Chem. 20, 3658-3665.
36. Yang, L., Li, L., Chen, L., Li, Y., Chen, H., Li, Y., Ji, G., Lin, D., Liu, Z., and Qiu, Y. (2015). Potential analgesic effects of a novel Nacylethanolamine acid amidase inhibitor F96 through PPAR-alpha. Sci. Rep. 5, 13565.
37. Ribeiro, A., Pontis, S., Mengatto, L., Armirotti, A., Chiurchiu, V., Capurro, V., Fiasella, A., Nuzzi, A., Romeo, E., Moreno-Sanz, G., Maccarrone, M., Reggiani, A., Tarzia, G., Mor, M., Bertozzi, F., Bandiera, T., and Piomelli, D. (2015). A potent systemically active Nacylethanolamine acid amidase inhibitor that suppresses inflammation and human macrophage activation. ACS Chem. Biol. 10, 1838-1846.
38. Benito, C., Tolon, R.M., Castillo, A.I., Ruiz-Valdepenas, L., Martinez- Orgado, J.A., Fernandez-Sanchez, F.J., Vazquez, C., Cravatt, B.F., and Romero, J. (2012). Beta-amyloid exacerbates inflammation in astrocytes lacking fatty acid amide hydrolase through a mechanism involving PPAR-alpha, PPAR-gamma and TRPV1, but not CB(1) or CB(2) receptors. Br. J. Pharmacol. 166, 1474-1489.
39. Rivera, P., Bindila, L., Pastor, A., Perez-Martin, M., Pavon, F.J., Serrano, A., de la Torre, R., Lutz, B., Rodriguez de Fonseca, F., and Suarez, J. (2015). Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context. Front. Cell Neurosci. 9, 98.
40. Peferoen, L.A., Vogel, D.Y., Ummenthum, K., Breur, M., Heijnen, P.D., Gerritsen, W.H., Peferoen-Baert, R.M., van der Valk, P., Dijkstra, C.D., and Amor, S. (2015). Activation status of human microglia is dependent on lesion formation stage and remyelination in multiple sclerosis. J. Neuropathol. Exp. Neurol. 74, 48-63.
41. Brahmachari, S., Fung, Y.K., and Pahan, K. (2006). Induction of glial fibrillary acidic protein expression in astrocytes by nitric oxide. J. Neurosci, 26, 4930-4939.
42. Carson, M.J., Thrash, J.C., and Walter, B. (2006). The cellular response in neuroinflammation: The role of leukocytes, microglia and astrocytes in neuronal death and survival. Clin. Neurosci. Res. 6, 237-245.
43. Genovese, T., Esposito, E., Mazzon, E., Di Paola, R., Meli, R., Bramanti, P., Piomelli, D., Calignano, A., and Cuzzocrea, S. (2008). Effects of palmitoylethanolamide on signaling pathways implicated in the development of spinal cord injury. J. Pharmacol. Exp. Ther. 326, 12-23.
44. Esposito, E., Impellizzeri, D., Mazzon, E., Paterniti, I., and Cuzzocrea, S. (2012). Neuroprotective activities of palmitoylethanolamide in an animal model of Parkinson-s disease. PLoS One 7, e41880.
45. Yune, T.Y., Lee, S.M., Kim, S.J., Park, H.K., Oh, Y.J., Kim, Y.C., Markelonis, G.J., and Oh, T.H. (2004). Manganese superoxide dismutase induced by TNF-beta is regulated transcriptionally by NFkappaB after spinal cord injury in rats. J. Neurotrauma 21, 1778-1794.
46. Massa, P.T., Aleyasin, H., Park, D.S., Mao, X., and Barger, S.W. (2006). NFkappaB in neurons? The uncertainty principle in neurobiology. J. Neurochem. 97, 607-618.
47. Bowie, A., and O-Neill, L.A. (2000). Oxidative stress and nuclear factor-kappaB activation: a reassessment of the evidence in the light of recent discoveries. Biochem. Pharmacol. 59, 13-23.
48. Ahmed, A.U., Sarvestani, S.T., Gantier, M.P., Williams, B.R., and Hannigan, G.E. (2014). Integrin-linked kinase modulates lipopolysaccharide- and Helicobacter pylori-induced nuclear factor kappaBactivated tumor necrosis factor-alpha production via regulation of p65 serine 536 phosphorylation. J. Biol. Chem. 289, 27776-27793.
49. Morgan, M.J., and Liu, Z.G. (2011). Crosstalk of reactive oxygen species and NF-kappaB signaling. Cell Res. 21, 103-115.
50. Blackwell, T.S., and Christman, J.W. (1997). The role of nuclear factor-kappa B in cytokine gene regulation. Am. J. Respir. Cell Mol. Biol. 17, 3-9.
51. Impellizzeri, D., Ahmad, A., Bruschetta, G., Di Paola, R., Crupi, R., Paterniti, I., Esposito, E., and Cuzzocrea, S. (2015). The antiinflammatory effects of palmitoylethanolamide (PEA) on endotoxininduced uveitis in rats. Eur. J. Pharmacol. 761, 28-35.