Protective effects of melatonin on the white matter damage of neonatal rats by regulating NLRP3 inflammasome activity

Objective The aim of the study was to investigate the protective effects and relevant mechanisms of melatonin on the white matter damage (WMD) caused by endotoxin and ischemic hypoxia in neonatal rats. Methods Seventy-two female neonatal rats (postnatal day 3) were randomly divided into the sham, melatonin-treated, and control groups (n = 24 for each group). The periventricular white matter was collected to evaluate the WMD and apoptosis. In addition, the reactive oxygen species (ROS) level was measured. The expression levels of nucleotide-binding domain-like receptor protein 3 (NLRP3), interleukin (IL)-1 beta, IL-18, pink1, parkin, Toll-like receptor (TLR)-4, and nuclear factor (NF)-kappa B were detected. Results Hematoxylin and eosin and terminal-deoxynucleoitidyl transferase mediated nick end labeling staining showed that the WMD, as well as cell degeneration, necrosis, and apoptosis in the control group, were more severe than those in the melatonin-treated group. Endotoxin and ischemic hypoxia upregulated the expression of NLRP3 and downstream inflammatory factors such as IL-1 beta and IL-18, which could be reversed by melatonin treatment. Melatonin increased mitochondrial autophagy marker (pink1 and parkin) expression in the white matter and reduced ROS production. Moreover, melatonin-reduced TLR4 and NF-kappa B expression. Conclusions Melatonin can inhibit the hyperactivity of NLRP3 inflammasomes by enhancing mitochondrial autophagy and inhibiting TLR4/NF-kappa B pathway activity. Thus, melatonin may be a promising treatment for alleviating the WMD caused by endotoxin and ischemic hypoxia in neonatal rats.

Automated summary

The study found that melatonin can inhibit the overactivation of NLRP3 inflammasomes by enhancing mitochondrial autophagy and inhibiting TLR4/NF-κB pathway activity, thus alleviating white matter damage caused by endotoxin and ischemic hypoxia in neonatal rats.