%0 Journal Article %1 Favrais2007 %A Favrais, G?raldine %A Schwendimann, Leslie %A Gressens, Pierre %A Leli?vre, Vincent %D 2007 %J Neurobiol Dis %K Animals; Animals, Newborn; Brain; Cerebral Palsy; Cyclooxygenase 2; Inhibitors; Dinoprostone; Disease Models, Animal; Drug Interactions; Excitatory Amino Acid Agonists; Female; Gene Expression Regulation, Enzymologic; Ibotenic Acid; Indomethacin; Interleukin-1beta; Mice; Neurotoxins; Pregnancy; Risk Factors; Sulfonamides %N 3 %P 496--505 %R 10.1016/j.nbd.2006.10.012 %T Cyclooxygenase-2 mediates the sensitizing effects of systemic IL-1-beta on excitotoxic brain lesions in newborn mice. %U http://dx.doi.org/10.1016/j.nbd.2006.10.012 %V 25 %X Epidemiological and experimental data implicate maternal-fetal infection and an associated increase in circulating cytokines in the etiology of cerebral palsy. We have previously shown that pretreatment of newborn mice with systemic interleukin-1-beta exacerbates ibotenate-induced excitotoxic brain lesions. Such lesions are consistent with those observed in cerebral palsy. The present study builds on this murine model to assess the role of cyclooxygenase in interleukin-1-beta-induced brain toxicity. Pups pretreated with interleukin-1-beta developed greater ibotenate-induced brain damage than controls, an effect blocked by the co-administration of nimesulide (cyclooxygenase-2 inhibitor) or indomethacin (cyclooxygenase-1 and -2 inhibitor). Cyclooxygenase inhibitor administration prevented the interleukin-1-beta-induced increase in the production of brain prostaglandin E(2) (a cyclooxygenase metabolite) and changes in the expression of brain interleukin-6, interleukin-18, tumor necrosis factor-alpha, and brain-derived neurotrophic factor. It also stimulated the expression of brain interleukin-10. Our data suggest that the sensitizing effects of circulating inflammatory cytokines on the brain are mediated by the inducible isoform cyclooxygenase-2, which generates excess prostaglandin E(2). Some of these deleterious effects could involve an autocrine/paracrine loop leading to a disruption of the balance between pro- and anti-inflammatory cytokines in the brain.

@article{Favrais2007, abstract = {Epidemiological and experimental data implicate maternal-fetal infection and an associated increase in circulating cytokines in the etiology of cerebral palsy. We have previously shown that pretreatment of newborn mice with systemic interleukin-1-beta exacerbates ibotenate-induced excitotoxic brain lesions. Such lesions are consistent with those observed in cerebral palsy. The present study builds on this murine model to assess the role of cyclooxygenase in interleukin-1-beta-induced brain toxicity. Pups pretreated with interleukin-1-beta developed greater ibotenate-induced brain damage than controls, an effect blocked by the co-administration of nimesulide (cyclooxygenase-2 inhibitor) or indomethacin (cyclooxygenase-1 and -2 inhibitor). Cyclooxygenase inhibitor administration prevented the interleukin-1-beta-induced increase in the production of brain prostaglandin E(2) (a cyclooxygenase metabolite) and changes in the expression of brain interleukin-6, interleukin-18, tumor necrosis factor-alpha, and brain-derived neurotrophic factor. It also stimulated the expression of brain interleukin-10. Our data suggest that the sensitizing effects of circulating inflammatory cytokines on the brain are mediated by the inducible isoform cyclooxygenase-2, which generates excess prostaglandin E(2). Some of these deleterious effects could involve an autocrine/paracrine loop leading to a disruption of the balance between pro- and anti-inflammatory cytokines in the brain.}, added-at = {2014-07-19T19:25:58.000+0200}, author = {Favrais, G?raldine and Schwendimann, Leslie and Gressens, Pierre and Leli?vre, Vincent}, biburl = {https://www.bibsonomy.org/bibtex/260d16f5d49df6935614d6b70d714282f/ar0berts}, doi = {10.1016/j.nbd.2006.10.012}, groups = {public}, interhash = {ed2c53ad26bf437142ac1893d2ef0e45}, intrahash = {60d16f5d49df6935614d6b70d714282f}, journal = {Neurobiol Dis}, keywords = {Animals; Animals, Newborn; Brain; Cerebral Palsy; Cyclooxygenase 2; Inhibitors; Dinoprostone; Disease Models, Animal; Drug Interactions; Excitatory Amino Acid Agonists; Female; Gene Expression Regulation, Enzymologic; Ibotenic Acid; Indomethacin; Interleukin-1beta; Mice; Neurotoxins; Pregnancy; Risk Factors; Sulfonamides}, month = Mar, number = 3, pages = {496--505}, pii = {S0969-9961(06)00284-1}, pmid = {17166728}, timestamp = {2014-07-19T19:25:58.000+0200}, title = {Cyclooxygenase-2 mediates the sensitizing effects of systemic IL-1-beta on excitotoxic brain lesions in newborn mice.}, url = {http://dx.doi.org/10.1016/j.nbd.2006.10.012}, username = {ar0berts}, volume = 25, year = 2007 }