Abstract: The blood–spinal cord barrier is crucial for preserving homeostasis of the central nervous system. After spinal cord injury, autophagic flux within endothelial cells is disrupted, compromising the integrity of the blood–spinal cord barrier. This disruption facilitates extensive infiltration of inflammatory cells, resulting in exacerbated neuroinflammatory responses, neuronal death, and impaired neuronal regeneration. Previous research has demonstrated that photobiomodulation promotes the regeneration of damaged nerves following spinal cord injury by inhibiting the recruitment of inflammatory cells to the injured site and restoring neuronal mitochondrial function. However, the precise mechanisms by which photobiomodulation regulates neuroinflammation remain incompletely elucidated. In this study, we established a mouse model of spinal cord injury and assessed the effects of photobiomodulation treatment. Photobiomodulation effectively cleared damaged mitochondria from endothelial cells in mice, promoting recovery of hindlimb motor function. Using microvascular endothelial bEnd.3 cells subjected to oxygen–glucose deprivation, we found that the effects of photobiomodulation were mediated through activation of the PINK1/ Parkin pathway. Additionally, photobiomodulation reduced mitochondrial oxidative stress levels and increased the expression of tight junction proteins within the blood–spinal cord barrier. Our findings suggest that photobiomodulation activates mitochondrial autophagy in endothelial cells through the PINK1/Parkin pathway, thereby promoting repair of the blood–spinal cord barrier following spinal cord injury. 

Key words: autophagy, blood–spinal cord barrier, endothelial cell, mitochondria, neuroinflammatory, photobiomodulation, PTEN-induced kinase 1, repair, spinal cord injury, tight junction