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4-氨基吡啶对电压门控钾通道的抑制作用在斑马鱼脊髓损伤恢复中的影响

Effect of Voltage-Gated K Channel Inhibition by 4-aminopyridine in Spinal Cord Injury Recovery in Zebrafish.

作者信息

Hoffman Payge M, Mruk Karen

机构信息

School of Pharmacy, University of Wyoming, Laramie, WY, USA.

Department of Pharmacology and Toxicology, East Carolina University, Greenville, North Carolina, USA.

出版信息

bioRxiv. 2024 Jul 18:2024.07.15.603582. doi: 10.1101/2024.07.15.603582.

Abstract

Spinal cord injury (SCI) affects between 250,000 to 500,000 individuals annually. After the initial injury, a delayed secondary cascade of cellular responses occurs causing progressive degeneration and permanent disability. One part of this secondary process is disturbance of ionic homeostasis. The K channel blocker, 4-aminopyridine (4-AP), is used clinically to alleviate symptoms of multiple sclerosis (MS). Several ongoing studies are being conducted to explore additional areas where 4-AP may have an effect, including stroke, traumatic brain injury, and nervous system recovery after SCI. The goal of our study was to determine whether 4-AP affects recovery from SCI in zebrafish (). Using the transgenic line , we created a spinal transection and tracked swim recovery. We found that constant treatment with 10 μM 4-AP increases swimming distance 40%. Live imaging demonstrated that treatment with 4-AP increases radial glial cells bridging at the site of injury in the presence of 4-AP. We conclude that 10 μM 4-AP is pro-regenerative after SCI.

摘要

脊髓损伤(SCI)每年影响25万至50万人。在初次损伤后,会发生延迟的继发性细胞反应级联,导致进行性退化和永久性残疾。这个继发性过程的一部分是离子稳态的紊乱。钾通道阻滞剂4-氨基吡啶(4-AP)在临床上用于缓解多发性硬化症(MS)的症状。目前正在进行几项研究,以探索4-AP可能产生作用的其他领域,包括中风、创伤性脑损伤以及脊髓损伤后的神经系统恢复。我们研究的目的是确定4-AP是否会影响斑马鱼脊髓损伤后的恢复。利用转基因品系,我们进行了脊髓横切并追踪游泳恢复情况。我们发现,用10 μM 4-AP持续治疗可使游泳距离增加40%。活体成像显示,在4-AP存在的情况下,用4-AP治疗可增加损伤部位的放射状胶质细胞桥接。我们得出结论,10 μM 4-AP在脊髓损伤后具有促进再生的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad8c/11275812/2af11191778d/nihpp-2024.07.15.603582v1-f0001.jpg

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