NR AIKB
AU Minghetti,L.; Greco,A.; Cardone,F.; Puopolo,M.; Ladogana,A.; Almonti,S.; Cunningham,C.; Perry,V.H.; Pocchiari,M.; Levi,G.
TI Increased brain synthesis of prostaglandin E2 and F2-isoprostane in human and experimental transmissible spongiform encephalopathies
QU Journal of Neuropathology and Experimental Neurology 2000 Oct; 59(10): 866-71
PT journal article
AB The levels of 2 arachidonic acid metabolites formed either by enzymatic activity of cyclooxygenase, i.e. prostaglandin E2 (PGE2), or by free radical-catalyzed peroxidation, i.e. F2-isoprostane 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), were measured in the CSF of subjects with sporadic and familial Creutzfeldt-Jakob disease (CJD) and in brain homogenates of scrapie-infected mice. The CSF levels of both metabolites were increased in sporadic CJD (n = 52) and familial CJD (n = 10) patients when compared with a group of patients with noninflammatory disorders. Similarly, PGE2 and 8-epi-PGF2alpha levels were higher in brain homogenates obtained from C57BL/6J mice infected with the ME7 scrapie strain than in brain homogenates from control animals. As PGE2 is 1 of the most abundant prostaglandins released during inflammation and 8-epi-PGF2alpha is a quantitative marker of lipid peroxidation, our results provide in vivo biochemical evidence for the occurrence of inflammation and oxidative stress in human and experimental transmissible spongiform encephalopathies (TSEs), a concept so far based mainly on histopathological and in vitro evidence. Interestingly, in sporadic CJD patients, high CSF levels of PGE2, but not 8-epi-PGF2alpha, correlated with short survival time, suggesting that the inflammatory response correlates with the clinical duration of disease.
MH Adult; Aged; Aged, 80 and over; Animal; Brain/*metabolism; Creutzfeldt-Jakob Syndrome/*metabolism/mortality; Dinoprost/*analogs & derivatives/*biosynthesis; Dinoprostone/*biosynthesis; F2-Isoprostanes; Female; Human; Isoenzymes/metabolism; Lipid Peroxidation/physiology; Male; Mice; Mice, Inbred C57BL; Microglia/enzymology; Middle Age; Prostaglandin-Endoperoxide Synthase/metabolism; Scrapie/*metabolism; Support, Non-U.S. Gov't; Survival Analysis
AD Laboratory of Pathophysiology, Istituto Superiore di Sanita, Rome, Italy.
SP englisch
PO USA