Published Online
on May 5, 2005

A more recent version of this article appeared on June 1, 2005

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Submitted on December 21, 2004
Accepted on March 1, 2005

Increased Plasma Levels of 15-Deoxy Prostaglandin J₂ Are Associated With Good Outcome in Acute Atherothrombotic Ischemic Stroke

Miguel Blanco MD, PhD; María Ángeles Moro PhD; Antonio Dávalos MD, PhD; Rogelio Leira MD, PhD; Mar Castellanos MD, PhD; Joaquín Serena MD, PhD; José Vivancos MD, PhD; Manuel Rodríguez-Yáñez MD; Ignacio Lizasoain MD, PhD; and José Castillo MD, PhD^*

From the Department of Neurology (M.B., R.L., M.R.-Y., J.C.), Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela; the Department of Pharmacology (M.A.M., I.L.), School of Medicine, University Complutense de Madrid, Madrid; the Department of Neurosciences (A.D.), Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona; the Department of Neurology (M.C., J.S.), Hospital Universitario Doctor Josep Trueta, Girona; and the Department of Neurology (J.V.), Hospital Universitario La Princesa, Madrid, Spain.

^* To whom correspondence should be addressed. E-mail: mecasti{at}usc.es.

Background and Purpose--The 15-deoxy prostaglandin J₂ (15-dPGJ₂) is an anti-inflammatory prostaglandin that has been proposed to be the endogenous ligand of peroxisome proliferator-activated receptor- (PPAR), a nuclear receptor that can exert potent anti-inflammatory actions by repressing inflammatory genes when activated. It has been suggested that 15-dPGJ₂ could be beneficial in neurological disorders in which inflammation contributes to cell death such as stroke.

Methods--We investigated the relationship between plasma levels of 15-dPGJ₂ and early neurological deterioration (END), infarct volume, and neurologic outcome in 552 patients with an acute stroke admitted within 24 hours after symptoms onset.

Results--Median [quartiles] plasma 15-dPGJ₂ levels on admission were significantly higher in patients than in controls (60.5 [11.2 to 109.4] versus 5.0 [3.8 to 7.2] pg/mL; P<0.0001). Levels of this prostaglandin were also significantly higher in patients with vascular risk factors (history of hypertension or diabetes) and with atherothrombotic infarcts (113.9 [81.6 to 139.7] pg/mL), than in those with lacunar (58.7 [32.7 to 86.2] pg/mL), cardioembolic (12.1 [6.5 to 39.2] pg/mL), or undetermined origin infarcts (11.4 [5.6 to 24.3] pg/mL) (P<0.0001). In the subgroup of patients with atherothrombotic infarcts, the adjusted odds ratio of END and poor outcome for 1 pg/mL increase in 15-dPGJ₂ were 0.95 (95% CI, 0.94 to 0.97) and 0.97 (95% CI, 0.96 to 0.98), respectively. In a generalized linear model, by 1 U increase in 15-dPGJ₂, there was a reduction of 0.47 mL (95% CI, 0.32 to 0.63) in the mean estimated infarct volume.

Conclusions--Increased plasma 15-dPGJ₂ concentration is associated with good early and late neurological outcome and smaller infarct volume. These findings suggest a neuroprotective effect of 15-dPGJ₂ in atherothrombotic ischemic stroke.

Key words: atherosclerosis • diabetes mellitus • hypertension • inflammation • stroke

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