A therapeutic time window for anti-CD 11d monoclonal antibody treatment yielding reduced secondary tissue damage and enhanced behavioral recovery following severe spinal cord injury.

OBJECT: The purpose of this study was to investigate the therapeutic time window for antiinflammatory treatment within the first 24 hours of spinal cord injury (SCI). The authors have shown that an anti-CD11d antibody treatment attenuates leukocyte infiltration and improves neurological function when administered beginning 2 hours after SCI. A more clinically relevant time for the initiation of treatment after SCI, however, is 6 or more hours postinjury. METHODS: In Study 1, the T-4 vertebrae in four groups of rats were injured by a 50-g clip-induced compression method, and the anti-CD11d antibody (1 mg/kg) was intravenously administered starting 2, 6, 12, or 24 hours postinjury. All groups received subsequent doses at 24 and 48 hours, and animals were killed at 72 hours. The anti-CD11d antibody treatment starting at 6 hours postinjury caused significant attenuation of leukocyte infiltration, reactive oxygen species-associated enzymes, and secondary tissue damage. Based on these findings, Study 2 included two groups of rats receiving the aforementioned injury and treatment beginning at 6 hours postinjury (with subsequent treatments at 24 and 48 hours) with the anti-CD11d or a control antibody (1B7); these rats were then observed for 5 weeks. Basso-Beattie-Bresnahan (BBB) scores were significantly higher in anti-CD11d-treated rats (mean BBB score 8.9 +/- 0.1) than controls (mean BBB score 7.7 +/- 0.1) 5 weeks postinjury. Increases in mean arterial pressure during colon distension were smaller in anti-CD11d-treated rats (19.5 +/- 3.7 mm Hg) than in controls (37.4 +/- 4.7 mm Hg). CONCLUSIONS: These findings suggest that antiinflammatory treatments that reduce secondary tissue damage after SCI may be delayed until 6 hours postinjury and still be effective.