Targeted Repair of Spinal Cord Injury Based on miRNA-124-3p-Loaded Mesoporous Silica Camouflaged by Stem Cell Membrane Modified with Rabies Virus Glycoprotein.

Spinal cord injury (SCI) has no effective treatment modalities. It faces a significant global therapeutical challenge, given its features of poor axon regeneration, progressive local inflammation, and inefficient systemic drug delivery due to the blood-spinal cord barrier (BSCB). To address these challenges, a new nano complex that achieves targeted drug delivery to the damaged spinal cord is proposed, which contains a mesoporous silica nanoparticle core loaded with microRNA and a cloaking layer of human umbilical cord mesenchymal stem cell membrane modified with rabies virus glycoprotein (RVG). The nano complex more readily crosses the damaged BSCB with its exosome-resembling properties, including appropriate size and a low-immunogenic cell membrane disguise and accumulates in the injury center because of RVG, where it releases abundant microRNAs to elicit axon sprouting and rehabilitate the inflammatory microenvironment. Culturing with nano complexes promotes axonal growth in neurons and M2 polarization in microglia. Furthermore, it showed that SCI mice treated with this nano complex by tail vein injection display significant improvement in axon regrowth, microenvironment regulation, and functional restoration. The efficacy and biocompatibility of the targeted delivery of microRNA by nano complexes demonstrate their immense potential as a noninvasive treatment for SCI.

A novel mouse model of central cord syndrome.

Patients with potential spinal stenosis are susceptible to central cord syndrome induced by blunt trauma. Suitable animal models are helpful for studying the pathogenesis and treatment of such injuries. In this study, we established a mouse model of acute blunt traumatic spinal cord injury by compressing the C6 spinal cord with 5 and 10 g/mm2 compression weights to simulate cervical central cord syndrome. Behavioral testing confirmed that this model exhibited the characteristics of central cord syndrome because motor function in the front paws was impaired, whereas basic motor and sensory functions of the lower extremities were retained. Hematoxylin-eosin staining showed that the diseased region of the spinal cord in this mouse model was restricted to the gray matter of the central cord, whereas the white matter was rarely affected. Magnetic resonance imaging showed a hypointense signal in the lesion after mild and severe injury. In addition, immunofluorescence staining showed that the degree of nerve tract injury in the spinal cord white matter was mild, and that there was a chronic inflammation reaction. These findings suggest that this mouse model of central cord syndrome can be used as a model for preclinical research, and that gray matter is most vulnerable to injury in central cord syndrome, leading to impaired motor function.