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Liver X receptor agonist treatment regulates inflammatory response after spinal cord trauma
Author(s) -
Paterniti Irene,
Genovese Tiziana,
Mazzon Emanuela,
Crisafulli Concetta,
Di Paola Rosanna,
Galuppo Maria,
Bramanti Placido,
Cuzzocrea Salvatore
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06471.x
Subject(s) - liver x receptor , agonist , inflammation , receptor , spinal cord , nitrotyrosine , endocrinology , medicine , microglia , nitric oxide synthase , chemistry , spinal cord injury , nuclear receptor , nitric oxide , transcription factor , biochemistry , psychiatry , gene
J. Neurochem. (2010) 112 , 611–624. Abstract Liver X receptor α (LXRα) and LXRβ are members of the nuclear receptor superfamily of ligand‐activated transcription factors. The aim of this study was to investigate the effects of T0901317, a potent LXR receptor ligand, in a mouse model of spinal cord injury (SCI). SCI was induced by the application of vascular clips (force of 24 g) to the dura via a four‐level T5–T8 laminectomy in mice. Treatment with T0901317, 1 and 6 h after the SCI, significantly decreased (i) the degree of spinal cord inflammation and tissue injury (histological score); (ii) neutrophil infiltration (myeloperoxidase activity); (iii) inducible nitric oxide synthase expression; (iv) nitrotyrosine, lipid peroxidation, and poly‐ADP‐ribose formation; (v) pro‐inflammatory cytokines expression; (vi) nuclear factor‐kappa B activation; and (vii) apoptosis (terminal deoxynucleotidyltransferase‐mediated UTP end labeling staining, FAS ligand, Bax, and Bcl‐2 expression). Moreover, T0901317 significantly ameliorated the loss of limb function (evaluated by motor recovery score). These data suggest that LXR ligand may be useful in the treatment of inflammation associated with SCI.