Abstract
Spinal cord injury (SCI), as a severe central nervous system injury, often leads to permanent neurological deficits, posing significant challenges to clinical treatment. In recent years, the reconstruction of the metabolic-nutritional microenvironment has been widely recognized as a crucial breakthrough for promoting nerve repair in SCI. This microenvironment encompasses multidimensional changes, such as metabolic regulation, nutritional factor supply, and mitochondrial energy metabolism, and plays a key regulatory role in inflammatory responses and cellular metabolic adaptation through coupling with the gut-spinal cord axis and immune cell metabolic reprogramming. Although related research has advanced significantly, the spatiotemporal dynamic characteristics and underlying mechanisms of the metabolic-nutritional microenvironment in SCI repair remain incompletely elucidated. This article systematically reviews the fundamental concepts of the metabolic-nutritional microenvironment and its dynamic changes during the acute, subacute, and chronic phases of SCI, focusing on the mechanisms governing neurogenesis, axonal growth, neural stem cell fate determination, and functional rehabilitation. Based on this, from multiple levels including mitochondrial energy metabolism, supply of nutritional factors, and the gut-spinal cord axis, we propose an integrated intervention framework of "metabolic-nutritional microenvironment reconstruction-inflammation relief-neurogenesis" and focus on specific strategies such as metabolism-targeted drugs, nutritional interventions, and microenvironment engineering (hydrogels, conductive scaffolds, nano-delivery systems), aiming to provide theoretical basis and translational directions for optimizing SCI treatment and promoting in-depth development in this field.