Melatonin exerts neuroprotective effects by attenuating astro- and microgliosis and suppressing inflammatory response following spinal cord injury

Abstract

Reactive gliosis and inflammatory reaction are common pathological change to spinal cord injury (SCI). Whereas, the effects of melatonin (MT) on the astro- and microgliosis and their related inflammatory response in the injured spinal cord are not fully understood. In this study, MT's effects on the accumulation and proliferation of microglia and astrocytes and their related inflammatory response were investigated in an acute SCI model. The effects of MT on oxidative stress, neuronal survival and behavioral performance were also tested. It was found that MT treatment significantly suppressed the accumulation and the proliferation of microglia and astrocytes. Quantitative PCR data showed that MT significantly down-regulated the pro-inflammatory markers iNOS, IL-1β and TNF-α expressions. The data showed that MT led to the rise in SOD, CAT and GSH-Px contents and the decrease in MDA content. Western blotting analysis verified that MT significantly down-regulated caspase-3, Bax and GFAP expressions, up-regulated Bcl-2 expression. Compared with the SCI vehicle-treated group, the SCI MT-treated group exhibited a greater Basso Mouse Scale (BMS) locomotor rating score. On the whole, these findings implied that MT exerts its neuroprotective effects by suppressing the accumulation and the proliferation of microglia and astrocytes and reducing the release of pro-inflammatory cytokines, which might be one of the underlying mechanisms of the MT's neuroprotective effect after SCI. Accordingly, MT may be a promising therapeutic candidate for acute SCI.