Investigating the blood-spinal cord barrier in preclinical models: a systematic review of in vivo imaging techniques.

Abstract

This study is a systematic review. To evaluate current in vivo techniques used in the investigation of the blood-spinal cord barrier (BSCB). Search of English language literature for animal studies that investigated the BSCB in vivo. Data extraction included animal model/type, protocol for BSCB evaluation, and study outcomes. Descriptive syntheses are provided. A total of 40 studies were included, which mainly investigated rodent models of experimental autoimmune encephalomyelitis (EAE) or spinal cord injury (SCI). The main techniques used were magnetic resonance imaging (MRI) and intravital microscopy (IVM). MRI served as a reliable tool to longitudinally track BSCB permeability changes with dynamic contrast enhancement (DCE) using gadolinium, or assess inflammatory infiltrations with targeted alternative contrast agents. IVM provided high-resolution visualization of cellular and molecular interactions across the microvasculature, commonly with either epi-fluorescence or two-photon microscopy. MRI and IVM techniques enabled the evaluation of therapeutic interventions and mechanisms that drive spinal cord dysfunction in EAE and SCI. A small number of studies demonstrated the feasibility of DCE-computed tomography, ultrasound, bioluminescent, and fluorescent optical imaging methods to evaluate the BSCB. Technique-specific limitations and multiple protocols for image acquisition and data analyses are described for all techniques. There are few in vivo investigations of the BSCB. Additional studies are needed in less commonly studied spinal cord disorders, and to establish standardized protocols for data acquisition and analysis. Further development of techniques and multimodal approaches could overcome current imaging limitations to the spinal cord. These advancements might promote wider adoption of techniques, and can provide greater potential for clinical translation.