Increasing studies have demonstrated the neuroprotective effect of melatonin in central nervous system (CNS) diseases. However, the potential application of melatonin in therapy of subarachnoid hemorrhage (SAH) is still unclear. This study explored the potential effect of melatonin on early brain injury (EBI) induced by SAH and investigated the underlying mechanisms. Adult rats were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 hr after SAH. The mortality, SAH grade, neurologic score, brain water content, and neuronal apoptosis were evaluated. To explore further mechanisms, changes in JAK1/STAT3 signaling pathway and the levels of apoptosis-associated proteins were also examined. The results suggest that melatonin improved the neurologic deficits and reduced the brain water content and neuronal apoptosis. In addition, The JAK1 inhibitor, Ruxolitinib, was applied to manipulate the proposed pathway. Mortality, neurological scores, brain edema, cell apoptosis, and the expression of JAK1, STAT3, and cleaved caspase-3 proteins were assayed after 24 h SAH. Melatonin significantly improved neurological function and reduced neuronal apoptosis and brain edema at 24 h after SAH. The level of JAK1 was markedly up-regulated. Additionally, the level of cleaved caspase-3 was decreased by melatonin treatment. The beneficial effects of melatonin in SAH rats were partially suppressed by Ruxolitinib. In summary, our results demonstrate that melatonin treatment attenuates EBI following SAH via the JAK1/STAT3 signaling pathway.
Keywords: JAK1/STAT3 signaling; Melatonin; cell cycle; early brain injury; subarachnoid hemorrhage.
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