Antiinflammatory but no neuroprotective effects of melatonin under clinical treatment conditions in rabbit models of bacterial meningitis

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 anti inflammatory effects but did not reduce neuronal injury in either a rabbit model of gram-positive Streptococcus pneumoniae or gram-negative Escherichia coli meningitis. (c) 2006 Wiley-Liss, Inc.