Subarachnoid hemorrhage(SAH)is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy.Nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3)inflammasome activation associated with the upregulation of apoptotic signaling pathway has been implicated in various inflammatory diseases including hemorrhagic insults.Melatonin is reported to possess substantial anti-inflammatory properties,which is beneficial for early brain injury(EBI)after SAH.However,the molecular This article is protected by copyright.All rights reserved.mechanisms have not been clearly identified. The current study was designed to investigate theprotective effects of melatonin against EBI induced by SAH and to elucidate the potential mechanisms. The adult mice were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 h after SAH. Melatonin was neuroprotective, as shown by increased survival rate,as well as elevated neurological score, greater survival of neurons, preserved brain glutathione levels and reduced brain edema, malondialdehyde concentrations, apoptotic ratio, and blood brain barrier (BBB) disruption. Melatonin also attenuated the expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved caspase-1, interleukin-1β(IL-1β), and interleukin-6 (IL-6); these changes were also associated with an increase in the anti-apoptotic factor (Bcl2) and reduction in the pro-apoptotic factor (Bim). In summary, our resultsdemonstrate that melatonin treatment attenuates the EBI following SAH by inhibiting NLRP3 inflammasome-associated apoptosis.
Melatonin Subarachnoid hemorrhage Early brain injury Inflammasome Nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3
Yushu Dong Chongxi Fan Wei Hu Shuai Jiang Zhiqiang Ma Xiaolong Yan Chao Deng Shouyin Di Zhenlong Xin Guiling Wu Yang Yang Russel J.Reiter Guobiao Liang
Department of Neurosurgery,General Hospital of Shenyang Military Area Command,83 Wenhua Road,Shenyan Department of Biomedical Engineering,The Fourth Military Medical University,169 Changle West Road,Xi Department of Biomedical Engineering,The Fourth Military Medical University,169 Changle West Road,Xi Department of Aerospace Medicine,The Fourth Military Medical University,169 Changle West Road,Xi”an Department of Thoracic Surgery,Tangdu Hospital,The Fourth Military Medical University,1 Xinsi Road,X Department of Cardiovascular Surgery,Xijing Hospital,The Fourth Military Medical University,127 Chan Department of Cellular and Structural Biology,UT Health Science Center,7703 Floyd Curl Drive,San Ant