Proteomic Profiling Unraveling the Role of Lactate Dehydrogenase a in Vascular Repair and Functional Recovery after Spinal Cord Injury

Spinal cord injury (SCI) leads to complex pathological cascades, including endothelial cell dysfunction and vascular degeneration. In this study, we employed label-free quantitative proteomics to profile spinal cord tissue following injury, and identify altered molecular pathways. Proteomic analysis identified lactate dehydrogenase A (LDHA) as significantly upregulated at day post-injury 7 (DPI-7) and a potential regulator of vascular endothelial growth factor (VEGF)-VEGFR2 signaling. Pharmacological inhibition of LDHA using FX-11 led to increased oxidative stress in endothelial cells, reduced cell proliferation, impaired angiogenesis, and aggravated neuronal damage at the lesion epicenter. These findings suggest that LDHA functions as a metabolic regulator supporting endothelial cell survival under injury conditions. Notably, systemic lactate treatment counteracted the detrimental effects of LDHA inhibition and promoted functional recovery post-SCI. Overall, this study identifies LDHA as a critical regulator of VEGF-VEGFR2 signaling post-SCI and proposes lactate treatment as a potential therapeutic strategy to enhance vascular repair.