Treatment with TO901317, a synthetic liver X receptor agonist, reduces brain damage and attenuates neuroinflammation in experimental intracerebral hemorrhage

Journal of Neuroinflammation

Volumn 13, Issue 1, 2016, Pages

  Wu, Chun Hu ^a   Chen, Chien Cheng ^b   Lai, Chai You ^a   Hung, Tai Ho ^c   Lin, Chao Chang ^b   Chao, Min ^a   Chen, Szu Fu ^a,b  

^a NATIONAL DEFENSE MEDICAL CENTER   (Taiwan)

^b CHENG HSIN GENERAL HOSPITAL   (Taiwan)

^c CHANG GUNG UNIVERSITY   (Taiwan)

Author keywords

Inflammation; Intracerebral hemorrhage; Liver X receptors; Microglia; Neuronal damage; TO901317

Indexed keywords

ABC TRANSPORTER A1; ALANINE AMINOTRANSFERASE; CD45 ANTIGEN; CHOLESTEROL; CREATININE; CYCLOOXYGENASE 2; GELATINASE B; HEMOGLOBIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 1BETA; INTERLEUKIN 6; LIVER X RECEPTOR ALPHA; LIVER X RECEPTOR BETA; MACROPHAGE INFLAMMATORY PROTEIN 2; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38; MONOCYTE CHEMOTACTIC PROTEIN 1; N (2,2,2 TRIFLUOROETHYL) N [4 (2,2,2 TRIFLUORO 1 HYDROXY 1 TRIFLUOROMETHYLETHYL)PHENYL]BENZENESULFONAMIDE; NITRIC OXIDE; STRESS ACTIVATED PROTEIN KINASE; TRANSCRIPTION FACTOR RELA; TRIACYLGLYCEROL; ANTIINFLAMMATORY AGENT; COLLAGENASE; FLUORINATED HYDROCARBON; LIVER X RECEPTOR; NEUROPROTECTIVE AGENT; SULFONAMIDE; TO-901317;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BLOOD BRAIN BARRIER DISRUPTION; BODY WEIGHT; BRAIN ATROPHY; BRAIN DAMAGE; BRAIN DISEASE; BRAIN EDEMA; BRAIN HEMORRHAGE; BRAIN WATER; CELL ACTIVATION; CELL DEATH; CELL INFILTRATION; CELLULAR DISTRIBUTION; COGNITION; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; MACROPHAGE; MALE; MICROGLIA; MOUSE; NERVOUS SYSTEM INFLAMMATION; NEUROPROTECTION; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; UREA NITROGEN BLOOD LEVEL; AGONISTS; ANIMAL; ANIMAL BEHAVIOR; BLOOD BRAIN BARRIER; BODY WATER; C57BL MOUSE; CHEMICALLY INDUCED; COMPLICATION; DRUG EFFECTS; GENE EXPRESSION REGULATION; INFLAMMATION; PSYCHOLOGY;

ANIMALS; ANTI-INFLAMMATORY AGENTS; BEHAVIOR, ANIMAL; BLOOD-BRAIN BARRIER; BODY WATER; CEREBRAL HEMORRHAGE; COLLAGENASES; GENE EXPRESSION REGULATION; HYDROCARBONS, FLUORINATED; INFLAMMATION; LIVER X RECEPTORS; MALE; MICE; MICE, INBRED C57BL; NEUROPROTECTIVE AGENTS; SULFONAMIDES;

EID: 84960369473     PISSN: None     EISSN: 17422094     Source Type: Journal    
DOI: 10.1186/s12974-016-0524-8     Document Type: Article

References (57)

1. Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5:53-63.
2. Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012;11:720-31.
3. MacLellan CL, Paquette R, Colbourne F. A critical appraisal of experimental intracerebral hemorrhage research. J Cereb Blood Flow Metab. 2012;32:612-27.
4. Fang HY, Ko WJ, Lin CY. Inducible heat shock protein 70, interleukin-18, and tumor necrosis factor alpha correlate with outcomes in spontaneous intracerebral hemorrhage. J Clin Neurosci. 2007;14:435-41.
5. Hou J, Manaenko A, Hakon J, Hansen-Schwartz J, Tang J, Zhang JH. Liraglutide, a long-acting GLP-1 mimetic, and its metabolite attenuate inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab. 2012;32:2201-10.
6. Lei B, Dawson HN, Roulhac-Wilson B, Wang H, Laskowitz DT, James ML. Tumor necrosis factor alpha antagonism improves neurological recovery in murine intracerebral hemorrhage. J Neuroinflammation. 2013;10:103.
7. Rolland WB, Lekic T, Krafft PR, Hasegawa Y, Altay O, Hartman R, et al. Fingolimod reduces cerebral lymphocyte infiltration in experimental models of rodent intracerebral hemorrhage. Exp Neurol. 2013;241:45-55.
8. Wang YC, Wang PF, Fang H, Chen J, Xiong XY, Yang QW. Toll-like receptor 4 antagonist attenuates intracerebral hemorrhage-induced brain injury. Stroke. 2013;44:2545-52.
9. Zhou Y, Wang Y, Wang J, Anne Stetler R, Yang QW. Inflammation in intracerebral hemorrhage: from mechanisms to clinical translation. Prog Neurobiol. 2014;115C:25-44.
10. Zelcer N, Tontonoz P. Liver X receptors as integrators of metabolic and inflammatory signaling. J Clin Invest. 2006;116:607-14.
11. Im SS, Osborne TF. Liver x receptors in atherosclerosis and inflammation. Circ Res. 2011;108:996-1001.
12. Beyea MM, Heslop CL, Sawyez CG, Edwards JY, Markle JG, Hegele RA, et al. Selective up-regulation of LXR-regulated genes ABCA1, ABCG1, and APOE in macrophages through increased endogenous synthesis of 24(S),25-epoxycholesterol. J Biol Chem. 2007;282:5207-16.
13. Hong C, Tontonoz P. Liver X receptors in lipid metabolism: opportunities for drug discovery. Nat Rev Drug Discov. 2014;13:433-44.
14. Kim OS, Lee CS, Joe EH, Jou I. Oxidized low density lipoprotein suppresses lipopolysaccharide-induced inflammatory responses in microglia: oxidative stress acts through control of inflammation. Biochem Biophys Res Commun. 2006;342:9-18.
15. Zelcer N, Khanlou N, Clare R, Jiang Q, Reed-Geaghan EG, Landreth GE, et al. Attenuation of neuroinflammation and Alzheimer's disease pathology by liver x receptors. Proc Natl Acad Sci U S A. 2007;104:10601-6.
16. Zhang-Gandhi CX, Drew PD. Liver X receptor and retinoid X receptor agonists inhibit inflammatory responses of microglia and astrocytes. J Neuroimmunol. 2007;183:50-9.
17. Cui W, Sun Y, Wang Z, Xu C, Peng Y, Li R. Liver X receptor activation attenuates inflammatory response and protects cholinergic neurons in APP/PS1 transgenic mice. Neuroscience. 2012;210:200-10.
18. Dai YB, Tan XJ, Wu WF, Warner M, Gustafsson JA. Liver X receptor beta protects dopaminergic neurons in a mouse model of Parkinson disease. Proc Natl Acad Sci U S A. 2012;109:13112-7.
19. Paterniti I, Genovese T, Mazzon E, Crisafulli C, Di Paola R, Galuppo M, et al. Liver X receptor agonist treatment regulates inflammatory response after spinal cord trauma. J Neurochem. 2010;112:611-24.
20. Morales JR, Ballesteros I, Deniz JM, Hurtado O, Vivancos J, Nombela F, et al. Activation of liver X receptors promotes neuroprotection and reduces brain inflammation in experimental stroke. Circulation. 2008;118:1450-9.
21. Chen J, Zacharek A, Cui X, Shehadah A, Jiang H, Roberts C, et al. Treatment of stroke with a synthetic liver X receptor agonist, TO901317, promotes synaptic plasticity and axonal regeneration in mice. J Cereb Blood Flow Metab. 2010;30:102-9.
22. Cheng O, Ostrowski RP, Liu W, Zhang JH. Activation of liver X receptor reduces global ischemic brain injury by reduction of nuclear factor-kappaB. Neuroscience. 2010;166:1101-9.
23. Sironi L, Mitro N, Cimino M, Gelosa P, Guerrini U, Tremoli E, et al. Treatment with LXR agonists after focal cerebral ischemia prevents brain damage. FEBS Lett. 2008;582:3396-400.
24. Chen J, Cui X, Zacharek A, Roberts C, Chopp M. eNOS mediates TO90317 treatment-induced angiogenesis and functional outcome after stroke in mice. Stroke. 2009;40:2532-8.
25. Beltowski J. Liver X receptors (LXR) as therapeutic targets in dyslipidemia. Cardiovasc Ther. 2008;26:297-316.
26. Chen M, Li X, Zhang X, He X, Lai L, Liu Y, et al. The inhibitory effect of mesenchymal stem cell on blood-brain barrier disruption following intracerebral hemorrhage in rats: contribution of TSG-6. J Neuroinflammation. 2015;12:61.
27. Wasserman JK, Zhu X, Schlichter LC. Evolution of the inflammatory response in the brain following intracerebral hemorrhage and effects of delayed minocycline treatment. Brain Res. 2007;1180:140-54.
28. Chang CF, Chen SF, Lee TS, Lee HF, Shyue SK. Caveolin-1 deletion reduces early brain injury after experimental intracerebral hemorrhage. Am J Pathol. 2011;178:1749-61.
29. Chen SF, Hsu CW, Huang WH, Wang JY. Post-injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injury. Br J Pharmacol. 2008;155:1279-96.
30. Chen SF, Tsai HJ, Hung TH, Chen CC, Lee CY, Wu CH, et al. Salidroside improves behavioral and histological outcomes and reduces apoptosis via PI3K/Akt signaling after experimental traumatic brain injury. PLoS ONE. 2012;7, e45763.
31. Wu CH, Hung TH, Chen CC, Ke CH, Lee CY, Wang PY, et al. Post-injury treatment with 7,8-dihydroxyflavone, a TrkB receptor agonist, protects against experimental traumatic brain injury via PI3K/Akt signaling. PLoS ONE. 2014;9, e113397.
32. Chen CC, Hung TH, Lee CY, Wang LF, Wu CH, Ke CH, et al. Berberine protects against neuronal damage via suppression of glia-mediated inflammation in traumatic brain injury. PLoS ONE. 2014;9, e115694.
33. Batchelor PE, Liberatore GT, Wong JY, Porritt MJ, Frerichs F, Donnan GA, et al. Activated macrophages and microglia induce dopaminergic sprouting in the injured striatum and express brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. J Neurosci. 1999;19:1708-16.
34. Wasserman JK, Schlichter LC. Minocycline protects the blood-brain barrier and reduces edema following intracerebral hemorrhage in the rat. Exp Neuro. 2007;207(2):227-37.
35. Sedgwick JD, Schwender S, Imrich H, Dorries R, Butcher GW, ter Meulen V. Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Proc Natl Acad Sci U S A. 1991;88:7438-42.
36. Ford AL, Goodsall AL, Hickey WF, Sedgwick JD. Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared. J Immunol. 1995;154:4309-21.
37. Koistinaho M, Koistinaho J. Role of p38 and p44/42 mitogen-activated protein kinases in microglia. Glia. 2002;40:175-83.
38. He Q, Pu J, Yuan A, Lau WB, Gao E, Koch WJ, et al. Activation of liver-X-receptor alpha but not liver-X-receptor beta protects against myocardial ischemia/reperfusion injury. Circ Heart Fail. 2014;7:1032-41.
39. Castrillo A, Joseph SB, Marathe C, Mangelsdorf DJ, Tontonoz P. Liver X receptor-dependent repression of matrix metalloproteinase-9 expression in macrophages. J Biol Chem. 2003;278:10443-9.
40. Wang YY, Dahle MK, Steffensen KR, Reinholt FP, Collins JL, Thiemermann C, et al. Liver X receptor agonist GW3965 dose-dependently regulates lps-mediated liver injury and modulates posttranscriptional TNF-alpha production and p38 mitogen-activated protein kinase activation in liver macrophages. Shock. 2009;32:548-53.
41. Fan X, Kim HJ, Bouton D, Warner M, Gustafsson JA. Expression of liver X receptor beta is essential for formation of superficial cortical layers and migration of later-born neurons. Proc Natl Acad Sci U S A. 2008;105:13445-50.
42. Kim HJ, Fan X, Gabbi C, Yakimchuk K, Parini P, Warner M, et al. Liver X receptor beta (LXRbeta): a link between beta-sitosterol and amyotrophic lateral sclerosis-Parkinson's dementia. Proc Natl Acad Sci U S A. 2008;105:2094-9.
43. Xu P, Xu H, Tang X, Xu L, Wang Y, Guo L, et al. Liver X receptor beta is essential for the differentiation of radial glial cells to oligodendrocytes in the dorsal cortex. Mol Psychiatry. 2014;19:947-57.
44. Repa JJ, Li H, Frank-Cannon TC, Valasek MA, Turley SD, Tansey MG, et al. Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouse. J Neurosci. 2007;27:14470-80.
45. Haase G, Pettmann B, Raoul C, Henderson CE. Signaling by death receptors in the nervous system. Curr Opin Neurobiol. 2008;18:284-91.
46. Wang J, Tsirka SE. Tuftsin fragment 1-3 is beneficial when delivered after the induction of intracerebral hemorrhage. Stroke. 2005;36:613-8.
47. Wu J, Yang S, Xi G, Song S, Fu G, Keep RF, et al. Microglial activation and brain injury after intracerebral hemorrhage. Acta Neurochir Suppl. 2008;105:59-65.
48. Solan PD, Piraino G, Hake PW, Denenberg A, O'Connor M, Lentsch A, et al. Liver X receptor alpha activation with the synthetic ligand T0901317 reduces lung injury and inflammation after hemorrhage and resuscitation via inhibition of the nuclear factor kappaB pathway. Shock. 2011;35:367-74.
49. Hong C, Kidani Y, A-Gonzalez N, Phung T, Ito A, Rong X, et al. Coordinate regulation of neutrophil homeostasis by liver X receptors in mice. J Clin Invest. 2012;122:337-47.
50. Woo MS, Park JS, Choi IY, Kim WK, Kim HS. Inhibition of MMP-3 or -9 suppresses lipopolysaccharide-induced expression of proinflammatory cytokines and iNOS in microglia. J Neurochem. 2008;106:770-80.
51. Chang JJ, Emanuel BA, Mack WJ, Tsivgoulis G, Alexandrov AV. Matrix metalloproteinase-9: dual role and temporal profile in intracerebral hemorrhage. J Stroke Cerebrovasc Dis. 2014;23:2498-505.
52. Power C, Henry S, Del Bigio MR, Larsen PH, Corbett D, Imai Y, et al. Intracerebral hemorrhage induces macrophage activation and matrix metalloproteinases. Ann Neurol. 2003;53:731-42.
53. Namjoshi DR, Martin G, Donkin J, Wilkinson A, Stukas S, Fan J, et al. The liver X receptor agonist GW3965 improves recovery from mild repetitive traumatic brain injury in mice partly through apolipoprotein E. PLoS ONE. 2013;8, e53529.
54. Koldamova RP, Lefterov IM, Staufenbiel M, Wolfe D, Huang S, Glorioso JC, et al. The liver X receptor ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease. J Biol Chem. 2005;280:4079-88.
55. Riddell DR, Zhou H, Comery TA, Kouranova E, Lo CF, Warwick HK, et al. The LXR agonist TO901317 selectively lowers hippocampal Abeta42 and improves memory in the Tg2576 mouse model of Alzheimer's disease. Mol Cell Neurosci. 2007;34:621-8.
56. Okabe A, Urano Y, Itoh S, Suda N, Kotani R, Nishimura Y, et al. Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell death. Redox Biol. 2013;2:28-35.
57. Gad SC. Animal models in toxicology. 2nd ed. Boca Raton: CRC/Taylor & Francis; 2007.