Spinal cord injury (SCI) is a devastating condition with a severe and lifelong impact on affected individuals. The severity and kind of functional impairment is influenced by the localization and size of tissue damage. This damage is primarily caused by the initial impact, but significantly enlarged by secondary damage mechanisms following the injury. These mechanisms include hemorrhage, apoptosis, oxidative stress, and inflammation. The inflammatory response has both beneficial and detrimental effects. We have identified a pro-inflammatory chemokine, CCL3 (Macrophage inflammatory protein 1-α, MIP-1α), as a critical factor after SCI.

Using a mouse model of lower thoracic SCI, we detected increased mRNA and protein expression of CCL3 and its receptors CCR5 and CCR1 after SCI. CCL3^−/−mice showed significant improvement of locomotor recovery, a smaller lesion size and reduced neuronal damage compared to wild-type controls. In addition, numbers of inflammatory cells and factors were markedly reduced in the absence of CCL3. Using a novel RNA inhibitor, we could also suppress CCL3 by intrathecal injection into the cerebrospinal fluid, resulting in similar impact on the inflammatory response.

In conclusion, we have identified CCL3 as a potential target to modulate the inflammatory response and secondary damage after SCI. Collectively, this study shows that CCL3 contributes to progressive tissue damage and functional impairment during secondary injury after SCI. Future questions include neuron specific and immune related mechanisms mediating tissue damage and functional impairment.