Blood–spinal cord barrier disruption after spinal cord injury: a time-dependent mechanistic review

Abstract

The blood–spinal cord barrier (BSCB) is a specialized vascular interface that preserves spinal cord homeostasis by regulating molecular and cellular trafficking between blood and neural tissue. Disruption of BSCB integrity is a critical pathological event follow-ing spinal cord injury (SCI), leading to increased permeability, inflammatory cell infil-tration, and secondary neurodegeneration. Increasing evidence indicates that BSCB breakdown is not a single event but a dynamic, time-dependent process. In this review, we summarize the molecular and cellular mechanisms responsible for BSCB disruption after SCI in a chronological manner. Key pathological events occurring during the acute, subacute, and chronic phases are discussed, including pathological hemody-namic changes, endothelial stress responses, epigenetic regulation, inflammatory me-diators, immune cell–endothelial interactions, and extracellular matrix remodeling. We further highlight endogenous protective and reparative mechanisms that emerge at later stages. A comprehensive understanding of the temporal characteristics of BSCB disruption may facilitate the development of phase-specific therapeutic strate-gies aimed at preserving barrier integrity, limiting secondary injury, and improving neurological recovery after SCI. This temporal perspective underscores the need for stage-specific interventions to preserve BSCB integrity and improve outcomes after SCI.