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丙戊酸介导的脊髓损伤后的神经保护和神经发生:从机制到临床潜力

Valproic acid-mediated neuroprotection and neurogenesis after spinal cord injury: from mechanism to clinical potential.

作者信息

Chu Tianci, Zhou Hengxing, Lu Lu, Kong Xiaohong, Wang Tianyi, Pan Bin, Feng Shiqing

机构信息

Department of Orthopaedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, PR China.

出版信息

Regen Med. 2015;10(2):193-209. doi: 10.2217/rme.14.86. Epub 2014 Dec 8.

Abstract

Spinal cord injury (SCI) is difficult to treat because of secondary injury. Valproic acid (VPA) is clinically approved for mood stabilization, but also counteracts secondary damage to functionally rescue SCI in animal models by improving neuroprotection and neurogenesis via inhibition of HDAC and GSK-3. However, a comprehensive review summarizing the therapeutic benefits and mechanisms of VPA for SCI and the issues affecting clinical trials is lacking, limiting future research on VPA and impeding its translation into clinical therapy for SCI. This article presents the current status of VPA treatment for SCI, emphasizing interactions between enhanced neuroprotection and neurogenesis. Crucial issues are discussed to optimize its clinical potential as a safe and effective treatment for SCI.

摘要

脊髓损伤(SCI)由于继发性损伤而难以治疗。丙戊酸(VPA)在临床上被批准用于稳定情绪,但在动物模型中,它还通过抑制组蛋白去乙酰化酶(HDAC)和糖原合成酶激酶-3(GSK-3)来改善神经保护和神经发生,从而对抗继发性损伤,在功能上挽救脊髓损伤。然而,目前缺乏一篇全面综述来总结VPA对脊髓损伤的治疗益处、作用机制以及影响临床试验的问题,这限制了未来对VPA的研究,并阻碍其转化为脊髓损伤的临床治疗方法。本文介绍了VPA治疗脊髓损伤的现状,强调增强神经保护和神经发生之间的相互作用。讨论了关键问题,以优化其作为脊髓损伤安全有效治疗方法的临床潜力。

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