Increased brain synthesis of prostaglandin E-2 and F-2-isoprostane in human and experimental transmissible spongiform encephalopathies
Minghetti, L., Greco, A., Cardone, F., Puopolo, M., Ladogana, A., Almonti, S., Cunningham, C., Perry, V.H., Pocchiari, M. and Levi, G. (2000) Increased brain synthesis of prostaglandin E-2 and F-2-isoprostane in human and experimental transmissible spongiform encephalopathies. Journal of Neuropathology & Experimental Neurology, 59, (10), 866-871.
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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 F2[alpha] (8-epi-PGF2[alpha]), 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-PGF2[alpha] 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-PGF2[alpha] 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-PGF2[alpha], correlated with short survival time, suggesting that the inflammatory response correlates with the clinical duration of disease.
|Subjects:||R Medicine > R Medicine (General)
Q Science > QR Microbiology
Q Science > QM Human anatomy
|Divisions:||University Structure - Pre August 2011 > School of Biological Sciences
|Date Deposited:||22 Aug 2008|
|Last Modified:||12 May 2013 01:18|
|Contributors:||Minghetti, L. (Author)
Greco, A. (Author)
Cardone, F. (Author)
Puopolo, M. (Author)
Ladogana, A. (Author)
Almonti, S. (Author)
Cunningham, C. (Author)
Perry, V.H. (Author)
Pocchiari, M. (Author)
Levi, G. (Author)
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