ABSTRACT
OBJECTIVE: Endotoxins, products of Gram-negative bacteria, are the primary cause of blood-brain barrier (BBB) damage. In the present study, we aimed to investigate the possible neuroprotection mechanisms of melatonin on BBB damage induced by endotoxemia. METHODS: Adult, female Sprague-Dawley rats (n = 42) were separated into four random groups as a control group and three treatment groups. Lipopolysaccharide (7,5 mg/kg/day) was administrated for a single dose to generate a 24-hour sepsis model on rats. Melatonin (10 mg/kg/day) was treated a week before sepsis. Afterward, the dissected brain tissues were examined by histopathological, biochemical, and molecular analyses. RESULTS: LPS caused weight loss in the groups. As a result, degenerated neurons with cytoplasmic vacuoles and irregular pyknotic nuclei, pale stained necrotic neurons, and vascular congestion were observed in LPS-exposed rats. However, MEL decreased the number of degenerated neurons in treated groups. MEL treatment increased ZO1 and Occludin immunoreactivity while decreasing TLR4 in brain tissues. MEL effect on protein expression was recorded for ZO1 increase and TLR4 decrease in brain tissue compared to LPS groups. MEL also decreased MDA levels in brain tissue. CONCLUSIONS: MEL recovered the degenerative damage of sepsis by contributing to blood-brain barrier integrity, and by decreasing inflammation, thus the neuroprotective effects of MEL might provide an experimental basis for clinical applications.
