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克仑司汀增强髓鞘形成,延缓轴突丢失,促进脊髓损伤的功能恢复。

Clemastine Enhances Myelination, Delays Axonal Loss and Promotes Functional Recovery in Spinal Cord Injury.

机构信息

Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, School of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China.

Department of Chongqing Emergency Medical Center, Chongqing University Center Hospital, School of Medicine, Chongqing University, Chongqing, 400014, China.

出版信息

Neurochem Res. 2022 Feb;47(2):503-515. doi: 10.1007/s11064-021-03465-0. Epub 2021 Oct 18.

Abstract

Recent evidence has shown that demyelination occurs along with axonal degeneration in spinal cord injury (SCI) during the secondary injury phase. Oligodendrocyte precursor cells (OPC) are present in the lesions but fail to differentiate into mature oligodendrocytes and form new myelin. Given the limited recovery of neuronal functions after SCI in adults without effective treatment available so far, it remains unknown whether enhancing OPC differentiation and myelination could benefit the recovery of SCI. To show the significance of myelin regeneration after SCI, the injury was treated with clemastine in the rat model. Clemastine is an FDA-approved drug that is potent in promoting oligodendrocyte differentiation and myelination in vivo, for four weeks following SCI. Motor function was assessed using sloping boards and grid walking tests and scored according to the Basso, Beattie, and Bresnahan protocol. The myelin integrity and protein expression were evaluated using transmission electron microscopy and immunofluorescence, respectively. The results indicated that clemastine treatment preserves myelin integrity, decreases loss of axons and improves functional recovery in the rat SCI model. The presented data suggest that myelination-enhancing strategies may serve as a potential therapeutic approach for the functional recovery in SCI.

摘要

最近的证据表明,在脊髓损伤(SCI)的继发性损伤阶段,脱髓鞘与轴突退变同时发生。少突胶质前体细胞(OPC)存在于病变部位,但未能分化为成熟的少突胶质细胞并形成新的髓鞘。由于目前尚无有效的治疗方法,成年人 SCI 后的神经元功能恢复有限,因此仍不清楚增强 OPC 分化和髓鞘形成是否有利于 SCI 的恢复。为了证明 SCI 后髓鞘再生的意义,在大鼠模型中用氯苯那敏治疗损伤。氯苯那敏是一种 FDA 批准的药物,在 SCI 后四周内具有促进体内少突胶质细胞分化和髓鞘形成的作用。使用斜板和网格行走测试评估运动功能,并根据 Basso、Beattie 和 Bresnahan 方案进行评分。使用透射电子显微镜和免疫荧光分别评估髓鞘完整性和蛋白质表达。结果表明,氯苯那敏治疗可保持髓鞘完整性,减少轴突丢失并改善大鼠 SCI 模型的功能恢复。所提供的数据表明,髓鞘增强策略可能是 SCI 功能恢复的一种潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69db/8827101/155587716437/11064_2021_3465_Fig1_HTML.jpg

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