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

TL;DR

This paper reviews how the blood-spinal cord barrier breaks down over time after spinal cord injury and how understanding this process could lead to better treatments.

Contribution

The paper provides a time-dependent mechanistic review of blood-spinal cord barrier disruption after spinal cord injury.

Findings

BSCB disruption is a dynamic, time-dependent process after SCI.

Key pathological events include hemodynamic changes, endothelial stress, and immune interactions.

Endogenous protective mechanisms emerge at later stages of injury.

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.

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