Radiation-induced edema is dependent on cyclooxygenase 2 activity in mouse brain.
Cerebrovascular dysfunction, characterized by compromise of the blood-brain barrier and formation of cerebral edema, is common during the acute period after brain irradiation and may contribute to delayed pathology (e.g. vascular collapse, white matter necrosis) that leads to functional deficits. Another response of normal brain tissue to radiation is the induction of inflammatory markers, such as cytokine expression and glial activation. In particular, radiation-induced neuroinflammation is associated with an elevation in cyclooxygenase 2 (COX2), one of two isoforms of the obligate enzyme in prostanoid synthesis and the principal target of non-steroid anti-inflammatory drugs. Since prostanoids serve as autocrine and paracrine mediators in numerous physiological and pathological processes, including vasoregulation, we investigated COX2 protein expression and COX2-mediated prostanoid production in radiation-induced cerebral edema in male C57/BL6 mice. We found that radiation induces COX2 protein that is accompanied by specific increases in prostaglandin E(2) and thromboxane A(2) within 4 and 24 h after brain irradiation. Furthermore, we showed that treatment with NS-398, a selective COX2 inhibitor, attenuated prostanoid induction and edema formation. These results suggest that radiation-induced changes in vascular permeability are dependent on COX2 activity, implicating this enzyme and its products as targets for potential therapeutic treatment/protection from the effects of radiation on normal brain tissue.
Moore
Amy H
AH
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, New York 14642, USA.
Olschowka
John A
JA
Williams
Jacqueline P
JP
Paige
Sharon L
SL
O'Banion
M Kerry
MK
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000528:radiation effects*; D001929:Brain Edema / Q000175:diagnosis / Q000201:enzymology* / Q000209:etiology*; D051546:Cyclooxygenase 2; D004307:Dose-Response Relationship, Radiation; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D011833:Radiation Injuries, Experimental / Q000201:enzymology / Q000209:etiology; D012720:Severity of Illness Index; D014018:Tissue Distribution
D007527:Isoenzymes; D011453:Prostaglandins; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases