Increased plasma levels of 15-deoxyDelta prostaglandin J2 are associated with good outcome in acute atherothrombotic ischemic stroke.
OBJECTIVE
The 15-deoxyDelta prostaglandin J2 (15-dPGJ2) is an anti-inflammatory prostaglandin that has been proposed to be the endogenous ligand of peroxisome proliferator-activated receptor-gamma (PPARgamma), 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.
Blanco
Miguel
M
Department of Neurology, Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain.
Moro
María Angeles
MA
Dávalos
Antonio
A
Leira
Rogelio
R
Castellanos
Mar
M
Serena
Joaquín
J
Vivancos
José
J
Rodríguez-Yáñez
Manuel
M
Lizasoain
Ignacio
I
Castillo
José
J
D000208:Acute Disease; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002545:Brain Ischemia / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007249:Inflammation; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000473:pathology; D016017:Odds Ratio; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000097:blood; D012044:Regression Analysis; D020521:Stroke / Q000097:blood* / Q000401:mortality / Q000628:therapy*; D013927:Thrombosis / Q000097:blood* / Q000401:mortality / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
C477819:15-deoxyprostaglandin J2; D000893:Anti-Inflammatory Agents; D008024:Ligands; D047495:PPAR gamma; D015230:Prostaglandin D2