Vascular Regeneration Following Spinal Cord Injury: Pathophysiology, Research Advances, and Therapeutic Innovations

Background and objectives: Mechanical injury of the spinal cord triggers a secondary complex long-term interplay of neural and vascular damage that obstructs neural regeneration and aggravates functional outcomes. Inherent vascular responses are often insufficient however; regulation of local revascularization pathways has shown promising potential in vascular and axonal restitution. This review delves into the pathophysiology of secondary processes and targeting approaches and highlights the advancements of angiogenesis in spinal cord injuries (SCI). The systematic review synthesizes research focusing on therapeutic innovations of vascular regeneration enhancement, providing the neuroprotective role of the vascular system and the potential of axonal regeneration.

Methods: This review summarizes the complex processes of the mechanical impact aftermath and the beneficial role of angiogenesis. The systematic search, according to PRISMA guidelines, was conducted by two observers in established MEDLINE databases. Included studies consisted of original research focusing on revascularization after SCI without time limitation. Literature or systematic reviews and non-English articles were excluded.

Results: After applying specific selection criteria, 113 studies were identified for providing original insights targeting angiogenesis in SCI. Typically, innate vascular response and endogenous angiogenesis are inadequate to confront the exacerbating inflammatory proliferation and vascular and neural disruption. Recent advancements and therapeutic innovations aim to enhance the angiogenic process mostly through augmentation of angiogenesis with proangiogenic factor administration or delivery through biomaterial. Moreover, genetic modulation, stem-cell therapies, and physical stimulation have shown promising results in improved vascularization and axonal recovery.

Conclusion: Spinal cord injuries prompt a critical need for treatments targeting vascular repair and blood-spinal cord barrier stabilization to support recovery. However, challenges persist in translating these strategies into clinical outcomes, primarily because of the incomplete understanding of the complex pathophysiology of SCI. Improving vascularization is crucial for minimizing secondary damage and promoting neural regeneration