Melatonin is neuroprotective in experimental Streptococcus pneumoniae meningitis

Abstract

Neuronal injury in bacterial meningitis is a consequence of the direct toxicity of bacterial components and inflammatory and oxidative mechanisms. Adjunctive therapy with melatonin was investigated in vitro and in experimental meningitis. Cellular damage was reduced by treatment with melatonin in organotypic hippocampal cultures (P < .001) and in human SH-SY5Y cells (P < .01). Rabbits were infected intracisternally with Streptococcus pneumoniae and received either melatonin (20 mg/kg body weight/24 h; n = 12) or saline (n = 11) intravenously. Twelve hours later, all rabbits received ceftriaxone (10 mg/kg body weight/h). The density of apoptotic dentate granule cells was lower in melatonin-treated rabbits (81.8 +/- 52.9 227.5 +/- 127.9 cells/ mm(2); P = .002). The activity of superoxide dismutase in the hippocampal formation was higher (P = .04), and nitrite concentrations in cerebrospinal fluid were lower, after treatment with melatonin (P = .003). Melatonin reduced neuronal injury in vitro and in experimental meningitis, and it may be suitable as adjunctive therapy in human meningitis.