Increased plasma levels of 15-deoxy Δ prostaglandin J2 are associated with good outcome in acute atherothrombotic ischemic stroke

Background and Purpose-The 15-deoxy Delta prostaglandin J(2) (15-dPGJ(2)) is an anti-inflammatory prostaglandin that has been proposed to be the endogenous ligand of peroxisome proliferator-activated receptor-gamma (PPAR gamma), a nuclear receptor that can exert potent anti-inflammatory actions by repressing inflammatory genes when activated. It has been suggested that 15-dPGJ(2) 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-dPGJ(2) 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-dPGJ(2), 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-dPGJ(2) concentration is associated with good early and late neurological outcome and smaller infarct volume. These findings suggest a neuroprotective effect of 15-dPGJ(2) in atherothrombotic ischemic stroke.