Role of endocannabinoids in neuron-glial crosstalk

Open Pain Journal

Volumn 3, Issue 1, 2010, Pages 29-36

  Luongo, Livio ^a   Palazzo, Enza ^a   de Novellis, Vito ^a   Maione, Sabatino ^a  

^a SECOND UNIVERSITY OF NAPLES   (Italy)

Author keywords

2 arachidonoylglycerol; Anandamide; Chronic pain; Endocannabinoids; Glia neuron crosstalk

Indexed keywords

2 ARACHIDONOYLGLYCEROL; ANANDAMIDE; CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; ENDOCANNABINOID; GUANINE NUCLEOTIDE BINDING PROTEIN;

ALLODYNIA; ARTICLE; ASTROCYTE; CATABOLISM; CELL TYPE; CHRONIC INFLAMMATION; CHRONIC PAIN; GLIA CELL; GLIOSIS; HUMAN; HYPERALGESIA; MICROGLIA; NERVE CELL; NERVE CELL PLASTICITY; NERVE INJURY; NEUROPATHIC PAIN; OLIGODENDROGLIA; PATHOPHYSIOLOGY; PRIORITY JOURNAL; SYNAPTOGENESIS;

EID: 77953746709     PISSN: None     EISSN: 18763863     Source Type: Journal    
DOI: 10.2174/1876386301003010029     Document Type: Article

References (118)

1. Bonica JJ. Pain-basic principles of management. Northwest Med 1970; 69(8): 567-8
2. Millan MJ.The induction of pain: an integrative review. Prog Neurobiol 1999; 57(1): 1-164.
3. Goya P, Jagerovic N, Hernandez-Folgado L, Martin MI. Cannabinoids and neuropathic pain. Mini Rev Med Chem 2003; 3(7): 765-72.
4. Cravatt BF, Lichtman AH. The endogenous cannabinoid system and its role in nociceptive behavior 2004. J Neuro Biol 2004; 61(1): 149-160.
5. Maione S, Bisogno T, de Novellis V, et al. Elevation of endocan-nabinoid levels in the ventrolateral periaqueductal grey through inhibition of fatty acid amide hydrolase affects descending nociceptive pathways via both cannabinoid receptor type 1 and transient receptor potential vanilloid type-1 receptors. J Pharmacol Exp Ther 2006; 316(3): 969-82.
6. Pertwee RG. Cannabinoid receptors and pain. Prog Neurobiol 2001; 63(5): 569-611.
7. Costa B, Trovato AE, Colleoni M, Giagnoni G, Zarini E, Croci T. Effect of the cannabinoid CB1 receptor antagonist, SR141716, on nociceptive response and nerve demyelination in rodents with chronic constriction injury of the sciatic nerve. Pain 2005; 116 (1-2): 52-61.
8. Palazzo E, de Novellis V, Petrosino S, et al. Neuropathic pain and the endocannabinoid system in the dorsal raphe: pharmacological treatment and interactions with the serotonergic system. Eur J Neurosci 2006; 24(7): 2011-20.
9. La Rana G, Russo R, Campolongo P, et al. Modulation of neuropathic and inflammatory pain by the endocannabinoid transport inhibitor AM404 [N-(4-hydroxyphenyl)-eicosa-5,8,11,14-tetraen-amide]. J Pharmacol Exp Ther 2006; 317(3): 1365-71.
10. Jhaveri MD, Sagar DR, Elmes SJ, Kendall DA, Chapman V. Cannabinoid CB2 receptor-mediated anti-nociception in models of acute and chronic pain. Mol Neurobiol 2007; 36(1): 26-35.
11. Petrosino S, Palazzo E, de Novellis V, et al. Changes in spinal and supraspinal endocannabinoid levels in neuropathic rats. Neuropharmacology 2007; 52(2): 415-22.
12. Watkins LR, Milligan ED, Maier SF.Spinal cord glia: new players in pain. Pain 2001; 93(3): 201-5.
13. Carlisle SJ, Marciano-Cabral F, Staab A, Ludwick C, Cabral GA. Differential expression of the CB2 cannabinoid receptor by rodent macrophages and macrophage-like cells in relation to cell activation. Intern Immunopharmacol 2002; 2: 69-82.
14. Klegeris A, Bissonnette CJ, McGeer PL. Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid-type CB2 receptor. Br J Pharmacol 2003; 139: 775-786.
15. Walter L, Franklin A, Witting A, et al. Non-psychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci 2003; 23: 1398-1405.
16. Rock RB, Gekker G, Hu S, et al. WIN55,212-2-mediated inhibition of HIV-1 expression in microglial cells: involvement of cannabinoid receptors. J Neuroimmune Pharmacol 2007; 2: 178-183.
17. Carrier EJ, Kearn CS, Barkmeier AJ, et al. Cultured rat microglial cells synthesize the endocannabinoid 2-arachidonylglycerol, which increases proliferation via a CB2 receptor-dependent mechanism. Mol Pharmacol 2004; 65(4): 999-1007.
18. Stella N. Endocannabinoid signaling in microglial cells. Neuro-pharmacology 2009; 56 Suppl 1: 244-53.
19. Anand P, Whiteside G, Fowler CJ, Hohmann AG. Targeting CB2 receptors and the endocannabinoid system for the treatment of pain. Brain Res Rev 2009; 60(1): 255-66. 2008.
20. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990; 346(6284): 561-4.
21. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993; 365(6441): 61-5.
22. Casu MA, Porcella A, Ruiu S, et al. Differential distribution of functional cannabinoid CB1 receptors in the mouse gastroenteric tract. Eur J Pharmacol 2003; 459(1): 97-105.
23. Lange JH, Kruse CG. Keynote review: Medicinal chemistry strategies to CB1 cannabinoid receptor antagonists. Drug Discov Today 2005; 10(10): 693-702.
24. Van Sickle MD, Duncan M, Kingsley PJ, et al. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 2005; 310(5746): 329-32.
25. Zhang J, Hoffert C, Vu HK, Groblewski T, Ahmad S, O'Donnell D. Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models. Eur J Neurosci 2003; 17(12): 2750-4.
26. Maresz K, Carrier EJ, Ponomarev ED, Hillard CJ, Dittel BN. Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J Neurochem 2005; 95(2): 437-45.
27. Racz I, Nadal X, Alferink J, et al. Crucial role of CB(2) cannabinoid receptor in the regulation of central immune responses during neuropathic pain. J Neurosci 2008; 28(46): 12125-35.
28. Luongo L, Palazzo E, Tambaro S, et al. 1-(2',4'-dichlorophenyl)-6-methyl-N-cyclohexylamine-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide, a novel CB2 agonist, alleviates neuropathic pain through functional microglial changes in mice. Neurobiol Dis 2010; 37: 177-85.
29. Johns DG, Behm DJ, Walker DJ, et al. The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. Br J Pharmacol 2007; 152: 825-831.
30. Lauckner JE, Jensen JB, Chen HY, Lu HC, Hille B, Mackie K. GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proc Natl Acad Sci USA 2008; 105: 2699-2704.
31. Oka S, Nakajima K, Yamashita A, Kishimoto S, Sugiura T. Identification of GPR55 as a lysophosphatidylinositol receptor. Biochem Biophys Res Comm 2007; 362: 928-934.
32. Waldeck-Weiermair M, Zoratti C, Osibow K, et al. Integrin clustering enables anandamide- induced Ca2 signaling in endothelial cells via GPR55 by protection against CB1-receptor-triggered repression. J Cell Sci 2008; 121: 1704-1717.
33. Jarai Z, Wagner JA, Varga K, et al. Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Proc Natl Acad Sci USA 1999; 96: 14136-14141.
34. Offertaler L, Mo F, Bátkai S, et al. Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor. Mol Pharmacol 2003; 63: 699-705.
35. Franklin A, Stella N. Arachidonylcyclopropylamide increases microglial cell migration through cannabinoid CB2 and abnormal-cannabidiol-sensitive receptors. Eur J Pharmacol 2003; 474: 195-198.
36. Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992; 258: 1946-1949.
37. Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2- monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995; 50: 83-90.
38. Bouaboula M, Poinot-Chazel C, Bourrié B, et al. Activation of mitogen-activated protein kinase by stimulation of the central can-nabinoid receptor CB1. Biochem J 1995; 312: 637-641.
39. Felder CC, Briley EM, Axelrod J, Simpson JT, Mackie K, Devane WA. Anandamide, an endogenous cannabimimetic eicosanoid, binds to the cloned human cannabinoid receptor and stimulates receptor-mediated signal transduction. Proc Natl Acad Sci USA 1993; 90: 7656-7660.
40. Vogel Z, Barg J, Levy R, Saya D, Heldman E, Mechoulam R. Anandamide, a brain endogenous compound, interacts specifically with the cannabinoid receptors and inhibits adenylate cyclase. J Neurochem 1993; 61: 352-355.
41. Cravatt BJ, Demarest K, Patricelli M, et al. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc Natl Acad Sci USA 2001; 98: 9371-9376.
42. Sugiura T, Kondo S, Sukagawa A, et al. 2-arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Comm 1995; 215: 89-97.
43. Stella N, Schweitzer P, Piomelli D. A second endogenous cannabi-noid that modulates long-term potentiation. Nature 1997; 388: 773-778.
44. Beltramo M, Piomelli D. Carrier-mediated transport and enzymatic hydrolysis of the endogenous cannabinoid 2-arachidonylglycerol. Neuropharmacology 2000; 11: 1231-1235.
45. Stella N, Piomelli D. Receptor-dependent formation of endogenous cannabinoids in cortical neurons. Eur J Pharmacol 2001; 425: 189-196.
46. Di Marzo V. Targeting the endocannabinoid system: to enhance or reduce? Nat Rev Drug Discov 2008; 7: 438-455.
47. Blankman JL, Simon GM, Cravatt BF. A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol. Chem Biol 2007; 14: 1347-1356.
48. Kozak KR, Rowlinson SW, Marnett LJ. Oxygenation of the endo-cannabinoid, 2-arachidonylglycerol, to glyceryl prostaglandins by cyclooxygenase-2. J Biol Chem 2000; 275: 33744-33749.
49. Dixon WE. The pharmacology of cannabis indica. Br Med J 1899; 2: 1354-7.
50. Thomas H. A community survey of adverse effects of cannabis use. Drug Alcohol Depend. 1996; 42(3): 201-7
51. Kalant H. Adverse effects of cannabis on health: an update of the literature since 1996. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28(5): 849-63.
52. Calignano A, La Rana G, Giuffrida A, Piomelli D. Control of pain initiation by endogenous cannabinoids. Nature 1998; 394: 277-281.
53. Clayton N, Marshall FH, Bountra C, O'Shaughnessy CT. CB1 and CB2 cannabinoid receptors are implicated in inflammatory pain. Pain 2002; 96: 253-260.
54. Cheng Y, Hitchcock SA. Targeting cannabinoid agonists for in-flammatory and neuropathic pain. Expert Opin Investig Drugs 2007; 16(7): 951-65.
55. Ibrahim MM, Deng H, Zvonok A, et al. Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: pain inhibition by receptors not present in the CNS. Proc Natl Acad Sci USA 2003; 100(18): 10529-33.
56. Ibrahim MM, Porreca F, Lai J, et al. CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opioids. Proc Natl Acad Sci USA 2005; 102(8): 3093-8.
57. Whiteside GT, Gottshall SL, Boulet JM, et al. A role for cannabinoid receptors, but not endogenous opioids, in the antinociceptive activity of the CB2-selective agonist, GW405833. Eur J Pharmacol 2005 28; 528(1-3): 65-72.
58. Valenzano KJ, Tafesse L, Lee G, et al. Pharmacological and pharmacokinetic characterization of the cannabinoid receptor 2 agonist, GW405833, utilizing rodent models of acute and chronic pain, anxiety, ataxia and catalepsy. Neuropharmacology 2005; 48(5): 658-72.
59. Beltramo M, Bernardini N, Bertorelli R, et al. CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms. Eur J Neurosci 2006; 23(6): 1530-8.
60. Romero-Sandoval A, Eisenach JC. Spinal cannabinoid receptor type 2 activation reduces hypersensitivity and spinal cord glial activation after paw incision. Anesthesiology 2007; 106(4): 787-794.
61. Romero-Sandoval A, Nutile-McMenemy N, DeLeo JA. Spinal microglial and perivascular cell cannabinoid receptor type 2 activation reduces behavioral hypersensitivity without tolerance after peripheral nerve injury. Anesthesiology 2008; 108(4): 722-734.
62. Bisogno T, Melck D, Bobrov MY, et al. N-acyl-dopamines: novel synthetic CB(1) cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo. Biochem J 2000; 351 Pt 3: 817-24
63. Huang SM, Bisogno T, Trevisani M, et al. An endogenous capsaicin-like substance with high potency at recombinant and native vanilloid VR1 receptors. Proc Natl Acad Sci USA 2002; 99(12): 8400-5
64. Di Marzo V. Endocannabinoids and other fatty acid derivates with cannabimimetic properties: biochemistry and possible physiopathological relevance. Bio Chim Biophys Acta 1998; 1392: 153-175.
65. Guasti L, Richardson D, Jhaveri M, et al. Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain. Mol Pain 2009; 5: 35.
66. Fetler L, Amigorena S. Neuroscience. Brain under surveillance: the microglia patrol. Science 2005; 309: 392-393.
67. Raivich G. Like cops on the beat: the active role of resting microglia. Trends Neurosci 2005; 28(11):571-3.
68. Garden GA, Moller T. Microglia biology in health and disease. J Neuroimmune Pharmacol 2006; 1: 127-137.
69. Trapp BD, Wujek JR, Criste GA, et al. Evidence for synaptic stripping by cortical microglia. Glia 2007; 55: 360-368.
70. Coyle DE. Partial peripheral nerve injury leads to activation of astroglia and microglia which parallels the development of allodynic behavior. Glia 1998; 23(1): 75-83.
71. Jin SX, Zhuang ZY, Woolf CJ, Ji RR. p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. J Neurosci 2003; 23(10): 4017-22.
72. Ledeboer A, Sloane EM, Milligan ED, et al. Minocycline attenuates mechanical allodynia and proinflammatory cytokine expression in rat models of pain facilitation. Pain 2005; 115(1-2): 71-83.
73. Olechowski CJ, Truong JJ, Kerr BJ. Neuropathic pain behaviours in a chronic-relapsing model of experimental autoimmune encepha-lomyelitis (EAE). Pain 2009; 141(1-2): 156-64.
74. Luongo L, Sajic M, Grist J, Clark AK, Maione S, Malcangio M. Spinal changes associated with mechanical hypersensitivity in a model of Guillain-Barré syndrome. Neurosci Lett 2008; 437(2): 98-102.
75. Medzhitov R. Origin and physiological roles of inflammation. Nature 2008; 454(7203): 428-35.
76. Milligan ED, Watkins LR. Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci 2009; 10(1): 23-36.
77. Abbadie C, Bhangoo S, De Koninck Y, Malcangio M, Melik-Parsadaniantz S, White FA. Chemokines and pain mechanisms. Brain Res Rev 2009; 60(1): 125-34.
78. Lever IJ, Bradbury EJ, Cunningham JR, et al. Brain-derived neurotrophic factor is released in the dorsal horn by distinctive patterns of afferent fiber stimulation. J Neurosci 2001; 21: 4469-4477.
79. Svensson CI, Hua XY, Protter AA, Powell HC, Yaksh TL. Spinal p38 MAP kinase is necessary for NMDA-induced spinal PGE(2) release and thermal hyperalgesia. Neuroreport 2003; 14: 1153-1157.
80. Taylor DL, Diemel LT, Pocock JM. Activation of microglial group III metabotropic glutamate receptors protects neurons against microglial neurotoxicity. J Neurosci 2003; 23(6): 2150-60.
81. Taylor DL, Jones F, Kubota ES, Pocock JM. Stimulation of microglial metabotropic glutamate receptor mGlu2 triggers tumor necrosis factor alpha-induced neurotoxicity in concert with microglial-derived Fas ligand. J Neurosci 2005; 25(11): 2952-6
82. Biber K, Laurie DJ, Berthele A, et al. Expression and signaling of group I metabotropic glutamate receptors in astrocytes and microglia. J Neurochem 1999; 72(4): 1671-80.
83. Milligan ED, Sloane EM, Watkins LR. Glia in pathological pain: a role for fractalkine. J Neuroimmunol 2008; 198: 113-120.
84. Bazan JF, Bacon KB, Hardiman G, et al. A new class of membrane-bound chemokine with a CX3C motif. Nature 1997; 385: 640-644.
85. Lindia JA, McGowan E, Jochnowitz N, Abbadie C. Induction of CX3CL1 expression in astrocytes and CX3CR1 in microglia in the spinal cord of a rat model of neuropathic pain. J Pain 2005; 6: 434-438.
86. Clark AK, Yip PK, Grist J, et al. Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain. Proc Natl Acad Sci USA 2007; 104: 10655-10660.
87. Zhuang ZY, Kawasaki Y, Tan PH, Wen YR, Huang J, Ji RR. Role of the CX3CR1/p38 MAPK pathway in spinal microglia for the development of neuropathic pain following nerve injury-induced cleavage of fractalkine. Brain Behav Immun 2007; 21: 642-651
88. Clark AK, Yip PK, Malcangio M. The liberation of fractalkine in the dorsal horn requires microglial cathepsin S. J Neurosci 2009; 29(21): 6945-54.
89. Cardona AE, Pioro EP, Sasse ME, et al. Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 2006; 9: 917-924.
90. Inoue K, Tsuda M, Tozaki-Saitoh H. Modification of neuropathic pain sensation through microglial ATP receptors. Purinergic Signal 2007; 3: 311-316.
91. Coull JA, Beggs S, Boudreau D, et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005; 438: 1017-1021.
92. Ulmann L, Hatcher JP, Hughes JP, et al. Up-regulation of P2X4 receptors in spinal microglia after peripheral nerve injury mediates BDNF release and neuropathic pain. J Neurosci 2008; 28: 11263-11268.
93. Tozaki-Saitoh H, Tsuda M, Miyata H, Ueda K, Kohsaka S, Inoue K. P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury. J Neurosci 2008; 28(19): 4949-56.
94. Kobayashi K, Yamanaka H, Fukuoka T, Dai Y, Obata K, Noguchi K. P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling and neuropathic pain. J Neurosci 2008; 28(11): 2892-902.
95. Haynes SE, Hollopeter G, Yang G, et al. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 2006; 9(12): 1512-9.
96. Orr AG, Orr AL, Li XJ, Gross RE, Traynelis SF. Adenosine A(2A) receptor mediates microglial process retraction. Nat Neurosci 2009; 12(7): 872-8.
97. Synowitz M, Glass R, Färber K, et al. A1 adenosine receptors in microglia control glioblastoma-host interaction. Cancer Res 2006; 66(17): 8550-7.
98. Hammarberg C, Schulte G, Fredholm BB. Evidence for functional adenosine A3 receptors in microglia cells. J Neurochem 2003; 86(4): 1051-4
99. Thacker MA, Clark AK, Bishop T, et al. CCL2 is a key mediator of microglia activation in neuropathic pain states. Eur J Pain 2009; 13: 263-272.
100. Abbadie C, Lindia JA, Cumiskey AM, et al. Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Proc Natl Acad Sci USA 2003; 100: 7947-7952.
101. Walter L, Franklin A, Witting A, Moller T, Stella N. Astrocytes in culture produce anandamide and other acylethanolamides. J Biol Chem 2002; 277: 20869-20876.
102. Panikashvili D, Simeonidou C, Ben-Shabat S, et al. An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 2001; 413(6855): 527-31.
103. Kreutz S, Koch M, Böttger C, Ghadban C, Korf HW, Dehghani F. 2-Arachidonoylglycerol elicits neuroprotective effects on excito-toxically lesioned dentate gyrus granule cells via abnormal-cannabidiol-sensitive receptors on microglial cells. Glia 2009; 7(3): 286-9
104. Witting A, Walter L, Wacker J, Moller T, Stella N. P2X7 receptors control 2-arachidonoylglycerol production by microglial cells. Proc Natl Acad Sci USA 2004; 101: 3214-3219.
105. Witting A, Chen L, Cudaback E, et al. Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection. Proc Natl Acad Sci USA 2006; 103: 6362-6367.
106. Areùvalo-Martin A, Vela JM, Molina-Holgado E, Borrell J, Guaza C. Therapeutic action of cannabinoids in a murine model of multiple sclerosis. J Neurosci 2003; 23: 2511-2516.
107. Navarrete CM, Fiebich BL, de Vinuesa AG, et al. Opposite effects of anandamide and N-arachidonoyl dopamine in the regulation of prostaglandin E and 8-iso-PGF formation in primary glial cells. J Neurochem 2009; 109(2): 452-64.
108. Correa F, Docagne F, Mestre L, et al. A role for CB2 receptors in anandamide signalling pathways involved in the regulation of IL-12 and IL-23 in microglial cells. Biochem Pharmacol 2009; 77(1): 86-100.
109. Correa F, Hernangómez M, Mestre L, et al. Anandamide enhances IL-10 production in activated microglia by targeting CB(2) receptors: Roles of ERK1/2, JNK, and NF-kappaB. Glia 2010; 58: 135-47.
110. Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 2009; 29: 13435-4.
111. Glezer A, Simard RS, Rivest S. Neuroprotective role of the innate immune system by microglia. Neuroscience 2007; 147: 867-883.
112. Elward K, Gasque P. "Eat me" and "don't eat me" signals govern the innate immune response and tissue repair in the CNS: emphasis on the critical role of the complement system. Mol Immunol 2003; 40: 85-94.
113. Blais V, Rivest S. Effects of TNF- and IFN- on nitric oxide-induced neurotoxicity in the mouse brain. J Immunol 2004; 172: 7043-7052.
114. Franklin A, Parmentier-Batteur S, Walter L, Greenberg DA, Stella N. Palmitoylethanolamide increases after focal cerebral ischemia and potentiates microglial cells motility. J Neurosci 2003; 23: 7767-7775.
115. Romero-Sandoval EA, Horvath R, Landry RP, DeLeo JA. Cannabinoid receptor type 2 activation induces a microglial anti-inflammatory phenotype and reduces migration via MKP induction and ERK dephosphorylation. Mol Pain 2009; 5: 25.
116. Romero J, Orgado JM. Cannabinoids and neurodegenerative diseases. CNS Neurol Disord Drug Targets 2009; 8: 440-50.
117. Garcia-Ovejero D, Arevalo-Martin A, Petrosino S, et al. The endo-cannabinoid system is modulated in response to spinal cord injury in rats. Neurobiol Dis 2009; 33: 57-71.
118. Totoiu MO, Keirstead HS. Spinal cord injury is accompanied by chronic progressive demyelination. J Comp Neurol 2005; 486: 373-383.