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.
%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
}