title: Antiinflammatory but no neuroprotective effects of melatonin under clinical treatment conditions in rabbit models of bacterial meningitis.
abstract: Neuronal injury is frequent in bacterial meningitis, resulting in a high rate of death and neurological sequelae. In a search of potential neuroprotective strategies for treatment of bacterial meningitis, the antioxidant melatonin was neuroprotective in cell culture experiments and in a rabbit Streptococcus pneumoniae meningitis model, when treatment was started at the time of infection. In the present study, adjunctive melatonin treatment applied from the beginning of antibiotic therapy 12 hr after infection at a dose of 1.67 mg/kg/hr resulted in plasma concentrations of 451 +/- 198 ng/ml, cerebrospinal fluid (CSF) concentrations of 154 +/- 57 ng/ml and a CSF-to-plasma ratio of 0.38 +/- 0.19 (mean +/- SD). Melatonin therapy had antiinflammatory effects but did not reduce neuronal injury in either a rabbit model of gram-positive Streptococcus pneumoniae or gram-negative Escherichia coli meningitis.
authors.affiliation: Department of Neurology, University Hospital, Georg-August-University of Göttingen, Göttingen, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Spreer
authors.forename: Joachim
authors.initials: J
authors.lastname: Gerber
authors.forename: Daniel
authors.initials: D
authors.lastname: Baake
authors.forename: Mareike
authors.initials: M
authors.lastname: Hanssen
authors.forename: Gerald
authors.initials: G
authors.lastname: Huether
authors.forename: Roland
authors.initials: R
authors.lastname: Nau
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D015232:Dinoprostone / Q000134:cerebrospinal fluid; D004195:Disease Models, Animal; D006624:Hippocampus / Q000382:microbiology / Q000473:pathology; D008550:Melatonin / Q000627:therapeutic use*; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid / Q000150:complications / Q000188:drug therapy*; D009474:Neurons / Q000187:drug effects; D011817:Rabbits; D018709:Statistics, Nonparametric; D013296:Streptococcus pneumoniae; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008550:Melatonin; D015232:Dinoprostone