Felodipine Promotes the Recovery of Mice With Spinal Cord Injury by Activating Macrolipophagy Through the AMPK-mTOR Pathway.

Spinal cord injury (SCI) is a serious clinical condition characterised by extensive mechanical damage that compromises the tissue structure and microenvironment of the affected area. This damage leads to the formation of fibrotic blood vessels and impaired energy metabolism, both of which hinder recovery. Felodipine, a clinically approved antihypertensive drug, acts as a selective calcium antagonist, primarily inhibiting extracellular calcium influx in arteriolar smooth muscle and selectively dilating arterioles. Additionally, felodipine has been demonstrated to induce autophagy. Considering these properties collectively, we hypothesised that felodipine could modulate the microenvironment of the injured spinal cord. In this study, we employed immunofluorescence and Western blot analyses to evaluate the effects of felodipine on microenvironment repair and neuroprotection, both in vitro and in vivo. Particular attention was given to its regulatory role in AMPK-mTOR pathway-mediated macrolipophagy. Our results demonstrated that felodipine effectively improved the injured spinal cord microenvironment by activating macrolipophagy, facilitating the clearance of myelin debris. Furthermore, felodipine promoted the restoration of endothelial cell tight junctions, thereby enhancing the integrity of the blood-spinal cord barrier. This attenuation of barrier disruption after SCI contributed to improved neuronal survival. These findings expanded the clinical application prospect of felodipine and presented new therapeutic avenues for treating SCI.