A technological platform to optimize combinatorial treatment design and discovery for chronic spinal cord injury

Chronic spinal cord injury (SCI) is associated with the development of serious medical concerns. In fact, it is increasingly well documented that most SCI patients who survive the first 24 hr will rapidly develop, within a few months to a few years, cardiovascular problems, type II diabetes, muscle wasting, osteoporosis, immune deficiencies, and other life-threatening problems. The cellular mechanisms underlying these so-called secondary health complications remain unclear, and no drug or standard approach has been developed to specifically treat these complications. To investigate the cellular and metabolic changes associated with chronic SCI and functional recovery, work mainly from our laboratory recently has led to the characterization of a mouse model of chronic paraplegia. This review reports cellular, systemic, and metabolic changes (associated mainly with secondary health complications) occurring within a few days to a few weeks after SCI in low-thoracic spinal cord-transected mice. We also describe our research platform developed to ease technological transfer and to accelerate drug-screening studies in animals. A global understanding of the many chronic changes occurring after SCI together with efficient tools and approaches for testing new or existing drug candidates is likely to yield the design of innovative treatments against secondary complications that combine cellular plasticity-modulating agents, locomotor network-activating drugs, hormonal therapy, and exercise training.