Spinal cord injury is accompanied by an initial inflammatory reaction followed by secondary injury that is caused, in part, by apoptosis. Recruitment of leukocytes from the blood compartment to the site of
inflammation in the injured spinal cord has been attributed to locally generated chemotactic agents (
cytokines and
chemokines). In addition to upregulation in the message levels of a number of
chemokines, we have found up-regulation in the message levels of several
chemokine receptors following
spinal cord contusion injury. To reduce the inflammatory response after
spinal cord injury, we have blocked the interaction of
chemokine receptors with their
ligands using the vMIPII
chemokine antagonist. Using a rat model of
spinal cord contusion injury, we show that continuous infusion of the antagonist for up to 7 days results in a decrease in infiltrating hematogenous cells at the site of injury. Histological evaluation ofthe tissue showed fewer activated macrophages at the site of injury. Concomitantly, reduced neuronal loss and
gliosis were observed in the antagonist infused spinal cord. In addition, increased expression of Bcl-2 gene, an endogenous inhibitor of apoptosis, was seen in the antagonist infused spinal cord at 7 days post injury. Morphologically, staining with the bisbenzamide
dye Hoechst 33342 showed significantly more apoptotic bodies in the vehicle compared to antagonist infused spinal cord. Our data suggest that
chemokine antagonist infusion post-injury results in limiting the inflammatory response following
spinal cord contusion injury, thereby attenuating neuronal loss, possibly due to decreased apoptosis. These findings support the contention that disrupting
chemokine interactions with their receptors may be an effective approach in reducing the secondary damage after
spinal cord injury.