Limiting spinal cord injury by pharmacological intervention

The direct primary mechanical trauma to neurons, glia and blood vessels that occurs with spinal cord injury (SCI) is followed by a complex cascade of biochemical and cellular changes which serve to increase the size of the injury site and the extent of cellular and axonal loss. The aim of neuroprotective strategies in SCI is to limit the extent of this secondary cell loss by inhibiting key components of the evolving injury cascade. In this review we will briefly outline the pathophysiological events that occur in SCI, and then review the wide range of neuroprotective agents that have been evaluated in preclinical SCI models. Agents will be considered under the following categories: antioxidants, erythropoietin and derivatives, lipids, riluzole, opioid antagonists, hormones, anti-inflammatory agents, statins, calpain inhibitors, hypothermia, and emerging strategies. Several clinical trials of neuroprotective agents have already taken place and have generally had disappointing results. In attempting to identify promising new treatments, we will therefore highlight agents with (1) low known risks or established clinical use, (2) behavioral data gained in clinically relevant animal models, (3) efficacy when administered after the injury, and (4) robust effects seen in more than one laboratory and/or more than one model of SCI.