Pharmacological treatment of acute spinal cord injury: how do we build on past success?
Most acute spinal cord injuries (SCI) do not involve complete transection of the spinal cord; typically, a rim of white matter survives. The potential for neurological recovery depends on optimal preservation of the ascending and descending white matter axons and their normal myelination. Pharmacologic strategies focus on the control of secondary injury processes, primarily lipid peroxidation (LP), and the salvage of as much white matter as possible. The first effective neuroprotective agent was methylprednisolone (MP), a glucocorticosteroid that in high doses improves neurological recovery in animals and humans following acute SCI. Tirilazad is a more targeted non-glucocorticoid LP inhibitor that has been shown to be neuroprotective and has fewer side effects than MP. Future SCI therapy is likely to encompass various neuroprotective agents, including inhibitors of LP, inhibitors of the nitric oxide-derived reactive oxygen species peroxynitrite, inhibitors of calpain (which is responsible for degrading the spinal cord cytoskeleton), and inhibitors of post-traumatic apoptosis of neurons and myelin-forming oligodendroglia. In addition, neuroprotective strategies will eventually be followed by neurorestorative agents that stimulate the plasticity of surviving neural pathways, and will be used in conjunction with other neurorestorative therapies like cell transplantation and gene therapy techniques.
Hall
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Pfizer Global Research and Development, Ann Arbor Laboratories, Michigan 48105, USA. edward.hall@pfizer.com
D000208:Acute Disease; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008775:Methylprednisolone / Q000378:metabolism / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*; D011281:Pregnatrienes / Q000378:metabolism / Q000627:therapeutic use; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism
D018696:Neuroprotective Agents; D011281:Pregnatrienes; D008775:Methylprednisolone; C053355:tirilazad