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

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 (Danio rerio). Using the transgenic line Tg(gfap:EGFP), 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.