Treatment with LXR agonists after focal cerebral ischemia prevents brain damage

Sironi, Luigi; Mitro, Nico; Cimino, Mauro; Gelosa, Paolo; Guerrini, Uliano; Tremoli, Elena; Saez, Enrique

doi:10.1016/j.febslet.2008.08.035

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Volume 582, Issue 23 , Pages 3396-3400, 15 October 2008

Treatment with LXR agonists after focal cerebral ischemia prevents brain damage

Edited by Laszlo Nagy

Luigi Sironi
- Department of Pharmacological Sciences, University of Milan,Via G. Balzaretti 9, 20133 Milan, Italy
- Monzino Cardiologic Center, IRCCS, Via Parea 4, 20138 Milan, Italy
- Equal contribution.
Nico Mitro
- Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, United States
- Department of Pharmacological Sciences, University of Milan,Via G. Balzaretti 9, 20133 Milan, Italy
- Equal contribution.
Mauro Cimino
- Institute of Pharmacology and Pharmacognosy, University of Urbino “Carlo Bo”, Via S. Chiara 27, 61029 Urbino (PU), Italy
Paolo Gelosa
- Department of Pharmacological Sciences, University of Milan,Via G. Balzaretti 9, 20133 Milan, Italy
Uliano Guerrini
- Department of Pharmacological Sciences, University of Milan,Via G. Balzaretti 9, 20133 Milan, Italy
Elena Tremoli
- Department of Pharmacological Sciences, University of Milan,Via G. Balzaretti 9, 20133 Milan, Italy
- Monzino Cardiologic Center, IRCCS, Via Parea 4, 20138 Milan, Italy
Enrique Saez
- Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, United States
- Corresponding author. Fax: +858 784 9440.

Received 27 June 2008; received in revised form 22 August 2008; accepted 30 August 2008. published online 10 September 2008.

Abstract

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.

Abbreviations: LXR, liver X receptor, ABCA1, ATP-binding cassette A1, SREBP, sterol regulated-element binding protein, MRI, magnetic resonance imaging

Keywords: Acute cerebral ischemia, Experimental therapy, Neuroprotection, Nuclear receptor, Transcriptional activator