REDUCTION OF CENTRAL-NERVOUS-SYSTEM REPERFUSION INJURY IN RABBITS USING DOXYCYCLINE TREATMENT

Background and Purpose Activated leukocytes appear to potentiate central nervous system reperfusion injury, and agents that block leukocyte adhesion have shown neuroprotective efficacy in experimental models. Doxycycline, a tetracycline antibiotic, inhibits leukocyte function in vitro, presumably through divalent cation binding. We used a model of focal central nervous system reperfusion injury to determine the efficacy of doxycycline treatment in preserving neurological function. Methods Rabbits randomly received 10 mg/kg IV doxycycline 30 minutes before ischemia (pretreatment group) or 45 minutes after ischemia (posttreatment group) or received phosphate-buffered saline vehicle (control group) followed by 10 mg/kg q 8 hours times two. The average length of reversible spinal cord ischemia required to produce paraplegia (P-50) at 18 hours was calculated for each group. Results For the control group (n=13), the P-50 was 22.8+/-2.2 minutes; for the pretreatment group (n=14), 35.5+/-2.4 minutes (P<.01; t=3.8); and for the posttreatment group (n=13), 31.4+/-4.2 minutes (not significant; t=1.6). Doxycycline also attenuated postischemic decreases in in vivo leukocyte counts and inhibited in vitro leukocyte adhesion. Therapeutic doxycycline levels at 24 hours were confirmed in the plasma and spinal cord. Conclusions This significant protective effect suggests that doxycycline, a safe and readily available agent, may play a role in reducing clinical central nervous system reperfusion injury.