Anti-Inflammatory Treatments during the Chronic Phase of Spinal Cord Injury Improve Locomotor Function in Adult Mice

Our previous data suggested that ongoing inflammation in the spinal cord 6 weeks following spinal cord injury was detrimental to locomotor function. Others have shown in the acute and sub-acute post-injury phase that microglial/macrophage activation and T regulatory cells are detrimental to recovery. Here, C57BL/6 mice with a moderately severe T9 contusion were injected intravenously daily with minocycline, which reduces microglial/macrophage activation, or with CD25 antibodies, which reduce T regulatory cell function, starting at 6 weeks after injury. Both anti-inflammatory drugs caused an improvement in hindlimb locomotor function over the 2-week treatment, as measured by the Basso Mouse Scale (BMS). The improvement was functionally important, with mice having problems with coordinated stepping (BMS similar to 6) before treatment to walking essentially normally (BMS > 7) at the end of the treatment. The effects diminished within 1 week after termination of the treatments, suggesting an ongoing and dynamic inflammatory process. The area of white matter or the inflammatory markers CD68 for activated microglia/macrophages and CD45 for leukocytes were not different between the groups. These data suggest that inflammation during the chronic phase following spinal cord injury reduces conduction through the epicenter, possibly by release of cytokines, and is amenable to treatment for improved neurological function.