Therapeutic Strategies Targeting Respiratory Recovery after Spinal Cord Injury: From Preclinical Development to Clinical Translation

卷:12

Review

关键词: TRANSCRANIAL MAGNETIC STIMULATION;    ACUTE INTERMITTENT HYPOXIA;    CHONDROITIN SULFATE PROTEOGLYCANS;    POSTTRAUMATIC-STRESS-DISORDER;    LONG-TERM FACILITATION;    2A RECEPTOR INHIBITION;    CENTRAL-NERVOUS-SYSTEM;    STEM-CELL GRAFTS;    FUNCTIONAL RECOVERY;    EXTRACELLULAR-MATRIX;   

DOI  :  10.3390/cells12111519

来源: SCIE

【 摘 要 】

High spinal cord injuries (SCIs) lead to permanent functional deficits, including respiratory dysfunction. Patients living with such conditions often rely on ventilatory assistance to survive, and even those that can be weaned continue to suffer life-threatening impairments. There is currently no treatment for SCI that is capable of providing complete recovery of diaphragm activity and respiratory function. The diaphragm is the main inspiratory muscle, and its activity is controlled by phrenic motoneurons (phMNs) located in the cervical (C3-C5) spinal cord. Preserving and/or restoring phMN activity following a high SCI is essential for achieving voluntary control of breathing. In this review, we will highlight (1) the current knowledge of inflammatory and spontaneous pro-regenerative processes occurring after SCI, (2) key therapeutics developed to date, and (3) how these can be harnessed to drive respiratory recovery following SCIs. These therapeutic approaches are typically first developed and tested in relevant preclinical models, with some of them having been translated into clinical studies. A better understanding of inflammatory and pro-regenerative processes, as well as how they can be therapeutically manipulated, will be the key to achieving optimal functional recovery following SCIs.