Chemokine antagonist infusion attenuates cellular infiltration following spinal cord contusion injury in rat

Spinal cord injury is accompanied by an initial inflammatory reaction follo wed 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 a gents (cytokines and chemokines). In addition to upregulation in the messag e levels of a number of chemokines, we have found up-regulation in the mess age levels of several chemokine receptors following spinal cord contusion i njury. To reduce the inflammatory response after spinal cord injury, we hav e blocked the interaction of chemokine receptors with their ligands using t he 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 in jury. Histological evaluation ofthe tissue showed fewer activated macrophag es 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 i n the antagonist infused spinal cord at 7 days post injury. Morphologically , staining with the bisbenzamide dye Hoechst 33342 showed significantly mor e apoptotic bodies in the vehicle compared to antagonist infused spinal cor d. Our data suggest that chemokine antagonist infusion post-injury results in limiting the inflammatory response following spinal cord contusion injur y, thereby attenuating neuronal loss, possibly due to decreased apoptosis. These findings support the contention that disrupting chemokine interaction s with their receptors may be an effective approach in reducing the seconda ry damage after spinal cord injury. Published 2000 Wiley-Liss, Inc.(dagger) .