Burn injury enhances brain prostaglandin E2 production through induction of cyclooxygenase-2 and microsomal prostaglandin E synthase in cerebral vascular endothelial cells in rats.
OBJECTIVE
To examine whether peripheral burn injury in rats elevates prostaglandin E2 in the central nervous system and to determine where in the central nervous system enzymes responsible for prostaglandin E2 synthesis are expressed.


METHODS
Prospective controlled animal study.


METHODS
University research laboratory.


METHODS
Sprague-Dawley rats.


METHODS
Rats received either approximately 25% full-thickness burn injury or sham treatment. At 36 hrs after the injury, the cerebrospinal fluid was sampled to measure prostaglandin E2, and the brain and the spinal cord were sampled for immunohistochemical detection of cyclooxygenase-2 and microsomal-type prostaglandin E2 synthase, enzymes that are responsible for prostaglandin E2 production.


RESULTS
The prostaglandin E2 concentration in the cerebrospinal fluid was significantly elevated in the injured rats, and this elevation was suppressed by a cyclooxygenase-2-specific inhibitor, NS398. Only in the injured rats, cyclooxygenase-2 and microsomal-type prostaglandin E synthase proteins were detected in vascular endothelial cells throughout the central nervous system with no regional difference. A double-immunofluorescence study revealed that cyclooxygenase-2 and microsomal-type prostaglandin E synthase were coexpressed in the perinuclear region of the endothelial cells.


CONCLUSIONS
These results indicate that peripheral burn injury induces cyclooxygenase-2 and microsomal-type prostaglandin E synthase in endothelial cells of the central nervous system. These enzymes likely elevate the cerebrospinal fluid concentration of prostaglandin E2, a prostanoid that, in turn, activates prostaglandin E2 receptors on the central nervous system neurons involved in the general symptoms following burn injury.
Ozaki-Okayama
Yoko
Y
Department of Anesthesiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Matsumura
Kiyoshi
K
Ibuki
Takae
T
Ueda
Masashi
M
Yamazaki
Yasuo
Y
Tanaka
Yoshifumi
Y
Kobayashi
Shigeo
S
D000210:Acute-Phase Reaction / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002056:Burns / Q000201:enzymology / Q000378:metabolism*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D011446:Prospective Studies; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric
D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone