Abstract
BACKGROUND: Spinal cord injury (SCI) has life-changing consequences, not just from the initial trauma, but also from a series of damaging processes that unfold afterwards, such as oxidative stress, inflammation, and nerve cell loss. At the heart of these events is the breakdown of the blood-spinal cord barrier (BSCB). When BSCB fails, harmful substances start flooding in, leading to progressive tissue damage. METHODS: In this review, we explore findings from 38 studies - including animal models and patient research - to shed light on how and why the BSCB fails after SCI, as well as what can be done to diagnose and treat this problem. The systematic review was registered with PROSPERO (ID No- 1173511). RESULTS: New diagnostic tools, like specialized MRI scans and blood or spinal fluid biomarkers, are helping doctors track changes in the BSCB. The causes of barrier breakdown are complex, involving oxidative stress, iron buildup, enzyme activity, genetic regulation, and immune responses, all of which make the injury worse over time. Promising treatments include a wide range from medicines and biological therapies to physical approaches like targeted exercise or nerve stimulation-all showing benefits in laboratory studies, though we still need more real-world evidence. CONCLUSIONS: Protecting BSCB represents a promising but underutilized treatment strategy for spinal cord injury. BSCB dysfunction is diffuse, persistent, and biologically reversible across acute-subacute stages, providing a rationale for stage-specific therapeutic targeting. Based on the latest research, we offer a practical pathway for doctors to detect and manage BSCB damage - matching the type of treatment to the stages of SCI recovery. Greater consistency in research, early clinical trials, and better use of new biomarkers will help move these therapies from the lab to everyday patient care. Ultimately, preserving the BSCB after injury is not just about protecting tissue - it's about giving people a better chance at recovery and a return to their lives.