Quercetin promotes angiogenesis and protects the blood-spinal cord barrier structure after spinal cord injury by targeting the PI3K/Akt signaling pathway

BACKGROUND: Revascularization and reconstruction of the blood-spinal cord barrier (BSCB) following spinal cord injury (SCI) play crucial roles in supplying essential nutrients and fostering a supportive microenvironment for neural network reconstruction. Thus, facilitating vascular regeneration and maintaining BSCB integrity are key therapeutic targets for functional recovery post-SCI. METHODS: Ischemia-induced pathological alterations in spinal cord microvascular endothelial cells were modeled in vitro using oxygen-glucose deprivation/reperfusion (OGD/R)-exposed bEnd.3 cells to assess whether QCT protects endothelial cells and enhances their angiogenic capacity. Subsequently, motor function, histopathological morphology, vascular density, and BSCB integrity were evaluated in rats with SCI to examine the therapeutic efficacy of QCT. A network pharmacology approach was employed to predict the potential pharmacological mechanisms of QCT in the treatment of SCI, followed by experimental validation. RESULTS: QCT enhanced survival, tube formation, and migration of bEnd.3 cells following OGD/R exposure in vitro. In the rat SCI model, QCT demonstrated beneficial effects on vascular regeneration and BSCB integrity, contributing to improved functional recovery. The PI3K/Akt signaling pathway was investigated to elucidate the underlying molecular mechanisms. CONCLUSIONS: These findings suggest that QCT can promote the regeneration of blood vessels in the injured spinal cord and protect the structure of the BSCB by activating the PI3K/Akt signaling pathway, thereby enhancing the neurological function of rats following SCI.