Hoffman Payge M, Mruk Karen
School of Pharmacy, University of Wyoming, Laramie, WY, USA.
Department of Pharmacology and Toxicology, East Carolina University, Greenville, North Carolina, USA.
bioRxiv. 2024 Jul 18:2024.07.15.603582. doi: 10.1101/2024.07.15.603582.
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.
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。