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In the present study, we investigated the implication of<jats:italic>Tpo<\/jats:italic>in experimental pneumococcal meningitis. Following intrathecal infection with the encapsulated<jats:italic>Streptococcus pneumoniae<\/jats:italic>strain D39, we observed upregulation of<jats:italic>Tpo<\/jats:italic>mRNA expression at 12 h and 24 h in brain homogenates of wild-type C57BL\/6 mice. c<jats:italic>-Mpl<\/jats:italic>mRNA expression was upregulated at 12 h and returned to baseline at 24 h. Compared to wild-type mice, mutants with homozygous Tpo receptor ablation (c<jats:italic>-Mpl<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) displayed reduced microglial activation and neuronal apoptosis in the dentate gyrus. Concentrations of bacteria in blood or cerebrospinal fluid (CSF), as well as CSF pleocytosis, were not significantly different between wild-type and c-<jats:italic>Mpl<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice. In human postmortem brain, Tpo protein was colocalized to macrophages during encephalitis. In murine primary microglia and RAW264.7 macrophages, upregulation of<jats:italic>Tpo<\/jats:italic>mRNA was induced by D39-conditioned medium but not by bacterial lipopeptide or by medium conditioned by pneumococcal mutants defective in hydrogen peroxide formation (\u0394<jats:italic>spxB<\/jats:italic>) or pneumolysin (\u0394<jats:italic>pln<\/jats:italic>). We conclude that Tpo acts as a mediator of neuronal damage in bacterial meningitis.<\/jats:p>","DOI":"10.1128\/iai.00782-10","type":"journal-article","created":{"date-parts":[[2010,12,14]],"date-time":"2010-12-14T04:43:35Z","timestamp":1292301815000},"page":"928-936","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Thrombopoietin Contributes to Neuronal Damage in Experimental Bacterial Meningitis"],"prefix":"10.1128","volume":"79","author":[{"given":"Olaf","family":"Hoffmann","sequence":"first","affiliation":[{"name":"Departments of Experimental Neurology, Charite\u0301\u2014Universita\u0308tsmedizin Berlin, Berlin, Germany"},{"name":"Department of Neurology, St. Josefs-Krankenhaus, Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Rung","sequence":"additional","affiliation":[{"name":"Departments of Experimental Neurology, Charite\u0301\u2014Universita\u0308tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ae-Rie","family":"Im","sequence":"additional","affiliation":[{"name":"Departments of Experimental Neurology, Charite\u0301\u2014Universita\u0308tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorette","family":"Freyer","sequence":"additional","affiliation":[{"name":"Departments of Experimental Neurology, Charite\u0301\u2014Universita\u0308tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Neonatology, Charite\u0301\u2014Universita\u0308tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephin","family":"Held","sequence":"additional","affiliation":[{"name":"Neuropathology, Charite\u0301\u2014Universita\u0308tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Stenzel","sequence":"additional","affiliation":[{"name":"Neuropathology, Charite\u0301\u2014Universita\u0308tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Dame","sequence":"additional","affiliation":[{"name":"Neonatology, Charite\u0301\u2014Universita\u0308tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.6.2162.bloodjournal8762162"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.134.2.351"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.2.448-455.1995"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00031-07"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12035"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-006-9149-0"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.3.923"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/mvre.1999.2161"},{"key":"e_1_3_2_10_2","first-page":"3509","volume":"55","year":"1995","unstructured":"Columbyova, L., M. 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