Treatment with LXR agonists after focal cerebral ischemia prevents brain damage.
Stroke is characterized by massive inflammation in areas surrounding the injury that magnifies damage to the brain. The liver X receptors (LXRs) are nuclear receptors that regulate cholesterol, lipid, and glucose metabolism. Synthetic LXR agonists have potent anti-inflammatory properties in a variety of settings, including neuroinflammation. However, the ability of LXR agonists to suppress stroke-associated inflammation has not been evaluated. Here, we have used time-lapse magnetic resonance imaging (MRI) to show that a single dose of an LXR ligand administered post-injury dramatically reduces brain damage in a model of acute brain ischemia. Neuroprotection was associated with suppression of neuroinflammation.
Sironi
Luigi
L
Department of Pharmacological Sciences, University of Milan,Via G. Balzaretti 9, 20133 Milan, Italy.
Mitro
Nico
N
Cimino
Mauro
M
Gelosa
Paolo
P
Guerrini
Uliano
U
Tremoli
Elena
E
Saez
Enrique
E
D000818:Animals; D001565:Benzoates / Q000627:therapeutic use*; D001596:Benzylamines / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004268:DNA-Binding Proteins / Q000819:agonists*; D004195:Disease Models, Animal; D008024:Ligands; D000071518:Liver X Receptors; D008279:Magnetic Resonance Imaging; D008297:Male; D057093:Orphan Nuclear Receptors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*
D001565:Benzoates; D001596:Benzylamines; D004268:DNA-Binding Proteins; C473027:GW 3965; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear
J Clin Invest. 2003 Jun;111(12):1843-51
12813020
Neuroscientist. 2007 Jun;13(3):208-13
17519364
Mol Cell. 2007 Jan 12;25(1):57-70
17218271
J Biol Chem. 2003 Mar 21;278(12):10443-9
12531895
EMBO J. 2006 Oct 4;25(19):4615-27
16990797
J Neurosci Res. 2007 Jan;85(1):73-82
17061257
J Clin Invest. 2006 Mar;116(3):607-14
16511593
J Cereb Blood Flow Metab. 1981;1(1):53-60
7328138
Mol Endocrinol. 2002 Jun;16(6):1378-85
12040022
Mol Neurodegener. 2007 Oct 22;2:20
17953774
Biochem Biophys Res Commun. 2006 Mar 31;342(1):9-18
16466690
Mol Med. 2007 Mar-Apr;13(3-4):125-33
17592546
Nat Med. 2003 Feb;9(2):213-9
12524534
Circulation. 2007 Feb 6;115(5):e69-171
17194875
Cell. 2004 Oct 15;119(2):299-309
15479645
Circulation. 2007 Sep 25;116(13):1504-14
17893286
Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):322-7
12588778
J Biol Chem. 2004 Mar 12;279(11):9905-11
14699103
Stroke. 2002 Mar;33(3):825-30
11872910
Stroke. 2005 Dec;36(12):2718-24
16282546
Annu Rev Physiol. 2006;68:159-91
16460270
Annu Rev Cell Dev Biol. 2004;20:455-80
15473848
Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10601-6
17563384