title: Dexamethasone increases hippocampal neuronal apoptosis in a rabbit model of Escherichia coli meningitis.
abstract: Mortality and long-term sequelae rates are high among adults and children with acute bacterial meningitis. Adjunctive treatment with dexamethasone has been shown to reduce systemic complications in bacterial meningitis patients, but corticosteroid treatment may have detrimental effects on hippocampal function. We evaluated the effect of dexamethasone treatment in addition to antibiotic therapy in a rabbit model of Escherichia coli meningitis. A moderate anti-inflammatory effect of dexamethasone could be demonstrated with respect to the inflammatory mediator prostaglandin E2, whereas no significant effect of dexamethasone on tumor necrosis factor-alpha, cerebrospinal fluid pleocytosis, protein, lactate, indicators of global neuronal damage, or blood gas analysis was found. Dexamethasone, however, increased the rate of apoptotic neurons in the granular layer of the hippocampal dentate gyrus. In view of the proapoptotic effect of adjunctive dexamethasone on hippocampal neuronal cells in animal models of Gram-positive and Gram-negative meningitis, the application of dexamethasone should be considered carefully in those forms of bacterial meningitis for which no evidence-based data of beneficial effect in humans are available, such as neonatal meningitis, bacillary Gram-negative meningitis or nosocomial forms of meningitis (e.g. following neurosurgery).
authors.affiliation: Department of Neurology, University Hospital, Georg-August-University of Göttingen, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Spreer
authors.forename: Joachim
authors.initials: J
authors.lastname: Gerber
authors.forename: Mareike
authors.initials: M
authors.lastname: Hanssen
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schindler
authors.forename: Corinna
authors.initials: C
authors.lastname: Hermann
authors.forename: Peter
authors.initials: P
authors.lastname: Lange
authors.forename: Helmut
authors.initials: H
authors.lastname: Eiffert
authors.forename: Roland
authors.initials: R
authors.lastname: Nau
mesh_terms: D000818:Animals; D017209:Apoptosis; D018891:Dentate Gyrus / Q000187:drug effects* / Q000473:pathology; D003907:Dexamethasone / Q000627:therapeutic use / Q000633:toxicity*; D015232:Dinoprostone / Q000134:cerebrospinal fluid; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007964:Leukocytosis / Q000134:cerebrospinal fluid; D020814:Meningitis, Escherichia coli / Q000188:drug therapy*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid
chemical_list: D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D015232:Dinoprostone