Therapeutic Approaches Targeting Vascular Repair After Experimental Spinal Cord Injury: A Systematic Review of the Literature

Abstract

Traumatic spinal cord injury (SCI) disrupts the spinal cord vasculature resulting in ischemia, amplification of the secondary injury cascade and exacerbation of neural tissue loss. Restoring functional integrity of the microvasculature to prevent neural loss and to promote neural repair is an important challenge and opportunity in SCI research. Herein, we summarize the course of vascular injury and repair following SCI and give a comprehensive overview of current experimental therapeutic approaches targeting spinal cord microvasculature to diminish ischemia and thereby facilitate neural repair and regeneration. A systematic review of the published literature on therapeutic approaches to promote vascular repair after experimental SCI was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. The MEDLINE databases PubMed, Embase, and OVID MEDLINE were searched using the keywords “spinal cord injury,” “angiogenesis,” “angiogenesis inducing agents,” “tissue engineering,” and “rodent subjects.” A total of 111 studies were identified through the search. Five main therapeutic approaches to diminish hypoxia-ischemia and promote vascular repair were identified as (1) the application of angiogenic factors, (2) genetic engineering, (3) physical stimulation, (4) cell transplantation, and (5) biomaterials carrying various factor delivery. There are different therapeutic approaches with the potential to diminish hypoxia-ischemia and promote vascular repair after experimental SCI. Of note, combinatorial approaches using implanted biomaterials and angiogenic factor delivery appear promising for clinical translation.

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AO Spine/Praxis Clinical Practice Guidelines for the Management of Acute Spinal Cord Injury: An Introduction to a Focus Issue

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Targeted Delivery of RGD-CD146+CD271+ Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Promotes Blood–Spinal Cord Barrier Repair after Spinal Cord Injury

“…Spinal cord injury (SCI) is a prevalent form of central nervous system trauma that can result in motor and sensory function loss, as well as adverse impacts on the physical and social well-being of patients . In cases of traumatic SCI, hypoxia induced by lesions can prompt endothelial cell malfunction, trigger the breakdown of the blood–spinal cord barrier (BSCB), and encourage the infiltration of various inflammatory cytokines, neutrophils, and macrophages into the injury region, leading to secondary damage. − In turn, secondary damage initiates a sequence of reactions, encompassing neuronal and glial cell death, inflammatory responses, and glial fibrosis scar formation, ultimately resulting in axonal regeneration failure . As such, the development of potential strategies to preserve the BSCB integrity represents a critical element in treating SCI.…”