Human spinal cord injury (SCI) is usually accompanied by persistent cord compression. Experimental data demonstrate that compression of the traumatized cord results in rapid neurological decline over hours. Undertaking decompression in humans within this time frame has proved impractical, with the time to surgery in studies of urgent decompression averaging between 10 and 24 h. There is, therefore, an important need for a therapy to prevent the neurological deterioration of patients prior to decompressive surgery. The aim of this study was to determine if hypothermia prevents compressive SCI, thereby limiting neurological decline. Rats were subjected to a moderate mid-thoracic SCI and spacers were inserted to compress the spinal cord by 45%. Decompression, by removal of the spacer, was performed immediately, and at 2 or 8 h post-injury. Hypothermia (33 degrees C) was commenced in half the animals at 30 mins post-injury and maintained for 7.5 h, with the other half remaining normothermic (37.3 degrees C). Motor recovery was assessed weekly, and the volume and area of tissue damage determined at the end of the 8-week study period. The results demonstrate that hypothermia significantly improves the behavioral and histological outcome of animals undergoing 8 h of compressive injury (the primary outcome measure). The hypothermia-treated group regained weight-supported locomotion (Basso-Beattie-Bresnahan [BBB] locomotor assessment score 9.5 +/- 0.9), while the normothermic group remained severely paraparetic (BBB score 5.3 +/- 0.6; p