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    Pneumococcal cell wall-induced meningitis impairs adult hippocampal neurogenesis (2007)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Hoffmann, Olaf
    Mahrhofer, Cordula
    Rueter, Nina
    Freyer, Dorette
    Bert, Bettina
    Fink, Heidrun
    Weber, Joerg R
    Quelle
    Infection and immunity; 75(9) — S. 4289–4297
    ISSN: 0019-9567
    Sprache
    Englisch
    Verweise
    Pubmed: 17591796
    Kontakt
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
    Tel.+49 30 838 53221 Fax.+49 30 838 53112
    email:pharmakologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Bacterial meningitis is a major infectious cause of neuronal degeneration in the hippocampus. Neurogenesis, a continuous process in the adult hippocampus, could ameliorate such loss. Yet the high rate of sequelae from meningitis suggests that this repair mechanism is inefficient. Here we used a mouse model of nonreplicative bacterial meningitis to determine the impact of transient intracranial inflammation on adult neurogenesis. Experimental meningitis resulted in a net loss of neurons, diminished volume, and impaired neurogenesis in the dentate gyrus for weeks following recovery from the insult. Inducible nitric oxide synthase (iNOS) immunoreactivity was prominent in microglia in nonproliferating areas of the dentate gyrus and hilus region after meningitis induction. Treatment with the specific iNOS inhibitor N6-(1-iminoethyl)-L-lysine restored neurogenesis in experimental meningitis. These data suggest that local central nervous system inflammation in and of itself suppresses adult neurogenesis by affecting both proliferation and neuronal differentiation. Repair of cognitive dysfunction following meningitis could be improved by intervention to interrupt these actively suppressive effects.