tion of oxygen supply) immediately after the injury is sustained to the subsequent edema, inflammation, and necrotic and apoptotic cell death and, later, to the formation of a glial scar, which can be a barrier to axon regeneration. To regain sensory and motor function, to prevent and eliminate pain, and to retrain and relearn motor tasks will almost certainly demand different treatment strategies and a combination of therapies.

A number of therapeutic interventions for spinal cord injuries have been explored over the past several decades. Advances have been made in emergency medical treatment and in rehabilitation efforts, and there is an increased understanding of the specific mechanisms and pathways that are targets for therapeutic interventions. Additionally, recent advances in neuroscience research are opening up new opportunities for the development of therapeutic approaches. Research toward addressing the consequences of spinal cord injuries focuses on a natural progression of strategies: preventing further tissue loss, maintaining the health of living cells, replacing cells that have died through apoptosis or necrosis, growing axons and ensuring functional connections, and strengthening and reestablishing synapses that restore the neural circuits required for functional recovery. These strategies lead to a range of therapeutic targets and priorities for spinal cord injury research (Table ES-1), each of which could theoretically be pursued together with others. For example, cell therapies that replace myelin could be combined with agents such as neurotrophic factors that promote axon regrowth.

One of the major challenges in developing combination therapies is determining those specific therapies that are safe for use in combination and that, in concert, will provide the greatest efficacy for the treatment of spinal cord injuries. Although it is possible for different combinations of drugs to be combined by trial and error, greater progress can be made if specific research efforts are devoted to developing and implementing a mechanism to select the most likely components that will be required for combination therapies. This requires a strategic approach to screening and assessing the potentials of the compounds and therapies to be used as components of combination therapies.

Much remains to be learned about the basic biology of spinal cord injuries and the numerous potential therapeutic targets involved in the complex processes of maintaining cell and tissue viability and promoting axonal growth and synaptic integrity that will result in improved and appropriate function in individuals with spinal cord injuries. Adding to the body of knowledge on neurological circuitry and mechanisms will be of benefit not only to improving function after a spinal cord injury but also to developing therapies for other neurological diseases and conditions.



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