Credit: CORBIS

The success of current approaches to promote recovery of motor function after spinal cord injury (SCI) is often very limited. Three studies using rodents now describe several potential new treatment strategies for SCI.

The role of infiltrating macrophages and resident microglia in the recovery from SCI has been controversial. Schwartz, Jung and collaborators developed a new method that allowed them to specifically assess the function of monocyte-derived infiltrating macrophages (MΦ) in recovery and to distinguish these cells from resident microglia at the lesion site in mice. They showed that blood-derived MΦ had infiltrated the SCI site 4 days after injury and that ablating these MΦ — which increased the number of activated resident microglia — diminished the (modest) recovery of locomotor ability. Conversely, increasing the numbers of infiltrating MΦ at the injury site resulted in fewer activated resident microglia and enhanced motor recovery. In addition, the authors showed that the MΦ produced interleukin-10 (IL-10), an anti-inflammatory cytokine that is essential for controlling the immune response to injury, at the injury site, and that IL-10-deficient MΦ failed to restore motor function. These findings suggest that infiltrating MΦ regulate the number of activated resident microglia and contribute to motor function recovery through IL-10 signalling.

Three studies using rodents now describe several potential new treatment strategies for SCI.

Neurotrophin 3 (NT3) was previously shown to promote axonal regeneration beyond the site of an SCI lesion, although the axons failed to reach their appropriate targets. Tuszynski and colleagues tested whether NT3 expression in the target area can act as a chemotropic cue for regenerating axons. Indeed, injection of an NT3-expressing lentivirus into the nucleus gracilis in the brainstem of SCI rats successfully guided axons to this target site, where axon terminals displayed ultrastructural features of synapses. However, regenerated axons were not myelinated and electrophysiological recordings did not detect synaptic activity.

Chondroitinase ABC (CHABC), which degrades components of the glial scar and perineuronal nets, has previously been shown to promote axonal growth and plasticity after SCI; however, by itself it failed to provide significant recovery of corticospinal function, although it helped more basic motor skills. Proposing that CHABC by itself might promote only random axonal connections, Fawcett and colleagues investigated recovery of motor function in mice with SCI that were treated with CHABC and also underwent task-specific rehabilitation (retrieving food pellets — a test for corticospinal function). This combined approach improved paw skills more than either strategy alone. However, the drawback of specifically improving one skill was that it reduced other motor skills, so rehabilitation in walking and climbing actually worsened skilled paw function.

These three studies demonstrate that different approaches for the repair of SCI can improve recovery. It is thought that a combination of various treatments might be able to boost recovery after SCI, and the hope is that these studies will lead to the refinement of current therapies.