From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.

Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

Who is who after spinal cord injury and repair? Can the brain stem descending motor pathways take control of skilled hand motor function?

Over the last years,anatomical,electrophysiological and genetic studies have carefully dissected the pathways connecting the brain and the spinal cord.Lawrence and Kuypers（1968）described the organization of the descending motor pathways in the non-human primate spinal cord.Although there are some differences between species regarding the precise anatomical location of each spinal pathway and the selective connectivity onto spinal interneurons and motoneurons, the pattern of organization described is con- served among the mammalian spinal cord （Courtine et al., 2007）. Based on their description, the major descending motor pathways are grouped depending on their anatomical origin and their termi- nal distribution pattern in the spinal grey matter. The motor cortex projects corticospinal axons to the spinal cord, which mostly run in the contralateral cord and innervate the mid and dorsal grey matter neurons.

Editor's Choice—Application of tissue-engineered materials in the repair of spinal cord injury

The development of tissue-engineered technology brings hope to the treatment of spinal cord injury. Preparation of a tissue-engineered spinal cord stent with three-dimensional bionic structure has important value in the construction of tissue-engineered spinal cord and the repair of spinal cord injury. Acellular scaffolds can be produced with chemical extraction,

A bioactive injectable self-healing anti-inflammatory hydrogel with ultralong extracellular vesicles release synergistically enhances motor functional recovery of spinal cord injury

The repair and motor functional recovery after spinal cord injury(SCI)remains a worldwide challenge.The inflammatory microenvironment is one of main obstacles on inhibiting the recovery of SCI.Using mesenchymal stem cells(MSCs)derived extracellular vesicles to replace MSCs transplantation and mimic cell paracrine secretions provides a potential strategy for microenvironment regulation.However,the effective preservation and controlled release of extracellular vesicles in the injured spinal cord tissue are still not satisfied.Herein,we fabricated an injectable adhesive anti-inflammatory F127-polycitrate-polyethyleneimine hydrogel(FE)with sustainable and long term extracellular vesicle release(FE@EVs)for improving motor functional recovery after SCI.The orthotopic injection of FE@EVs hydrogel could encapsulate extracellular vesicles on the injured spinal cord,thereby synergistically induce efficient integrated regulation through suppressing fibrotic scar formation,reducing inflammatory reaction,promoting remyelination and axonal regeneration.This study showed that combining extracellular vesicles into bioactive multifunctional hydrogel should have great potential in achieving satisfactory locomotor recovery of central nervous system diseases.