Our previous study showed that
lipopolysaccharide (LPS)-induced
brain injury in the neonatal rat is associated with nitrosative and oxidative stress. The present study was conducted to examine whether
melatonin, an endogenous molecule with
antioxidant properties, reduces systemic LPS-induced nitrosative and oxidative damage in the neonatal rat brain. Intraperitoneal (i.p.) injection of LPS (2mg/kg) was administered to Sprague-Dawley rat pups on postnatal day 5 (P5), and i.p. administration of
melatonin (20mg/kg) or vehicle was performed 5min after LPS injection. Sensorimotor behavioral tests were performed 24h after LPS exposure, and
brain injury was examined after these tests. The results show that systemic LPS exposure resulted in impaired sensorimotor behavioral performance, and
acute brain injury, as indicated by the loss of oligodendrocyte immunoreactivity and a decrease in mitochondrial activity in the neonatal rat brain.
Melatonin treatment significantly reduced LPS-induced neurobehavioral disturbances and brain damage in neonatal rats. The
neuroprotective effect of
melatonin was associated with attenuation of LPS-induced nitrosative and oxidative stress, as indicated by the decreased
nitrotyrosine- and 4-hydroxynonenal-positive staining in the brain following
melatonin and LPS exposure in neonatal rats. Further,
melatonin significantly attenuated LPS-induced increases in the number of activated microglia in the neonatal rat brain. The protection provided by
melatonin was also associated with a reduced number of
inducible nitric oxide synthase (iNOS)+ cells, which were double-labeled with ED1 (microglia). Our results show that
melatonin prevents the
brain injury and neurobehavioral disturbances induced by systemic LPS exposure in neonatal rats, and its
neuroprotective effects are associated with its impact on nitrosative and oxidative stress.