ABSTRACT
Introduction: Traumatic Spinal Cord Injury (SCI) is one of the leading causes of disability in the world. Treatment is limited to supportive care and no curative therapy exists. Experimental research to understand the complex pathophysiology and potential mediators of spinal cord regeneration is essential to develop innovative translational therapies. A multitude of experimental imaging methods to monitor spinal cord regeneration in vivo have developed over the last years. However, little literature exists to deal with advanced imaging methods specifically available in SCI research. Research Question: This systematic literature review examines the current standards in experimental imaging in SCI allowing for in vivo imaging of spinal cord regeneration on a neuronal, vascular, and cellular basis. Material and Methods: Articles were included meeting the following criteria: experimental research, original studies, rodent subjects, and intravital imaging. Reviewed in detail are microstructural and functional Magnetic Resonance Imaging, Micro-Computed Tomography, Laser Speckle Imaging, Very High Resolution Ultrasound, and in vivo microscopy techniques. Results: Following the PRISMA guidelines for systematic reviews, 689 articles were identified for review, of which 492 were sorted out after screening and an additional 104 after detailed review. For qualitative synthesis 93 articles were included in this publication. Discussion and Conclusion: With this study we give an up-to-date overview about modern experimental imaging techniques with the potential to advance the knowledge on spinal cord regeneration following SCI. A thorough knowledge of the strengths and limitations of the reviewed techniques will help to optimally exploit our current experimental armamentarium in the field.
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.
