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Activation of CREB-binding protein ameliorates spinal cord injury in tabersonine treatment by suppressing NLRP3/Notch signaling

作者:Yu Chuan, Yu Wang, Xu Jin, Shi Ming, Wan Bing, Kai Wu, Xiang Chen, Peng Kun · 发表于:Archives of Medical Science · 年份:2019 · DOI:10.5114/aoms.2019.89203 · 被引用次数:7 · 研究领域:Spinal Cord Injury Research、Spinal Dysraphism and Malformations、Cervical and Thoracic Myelopathy

Introduction: Spinal cord injury (SCI) alters the integrity of the spinal cord, which leads to loss of multiple organs' function including locomotor function. The present study evaluates the protective effect of tabersonine against SCI. Material and methods: SCI was induced by traumatic injury and animals were treated with tabersonine 20 and 40 mg/kg, intraperitoneally for the period of 10 days. Tabersonine's effect was determined by estimating locomotor and neurological function in spinal cord injured rats. Moreover, mediators of inflammation were estimated using enzyme-linked immunosorbent assay (ELISA) and the effect of tabersonine on Notch/inflammasome signaling was estimated by reverse transcription polymerase chain reaction (RT-PCR), western blot assay and immunohistochemistry. Apoptosis of neuronal cells was estimated by staining with Nissl stain on spinal cord tissue in SCI rats. Results: Data of the study suggest that neurological and motor functions were improved in the tabersonine treated group compared to the spinal cord injured (SI) group. There was a decrease in the mediators of inflammation in the spinal cord tissue of the tabersonine treated group compared to the SI group. Treatment with tabersonine ameliorates the altered expression of NICD, Nestin and Hes-1 protein and mRNA expression of Notch-1 and Hes-1 in the SCI rats. It was also observed that the tabersonine treated group showed activation of CREB and inhibition of the NLRP-3 pathway in SCI rats. Moreov...