Extracellular non-
adenine based
purines are neuroprotective. Preliminary studies indicate that administration of the synthetic
purine 4-[[3-(1,6 dihydro-6-oxo-9-
purine-9-yl)-1-oxypropyl] amino]
benzoic acid (
AIT-082,
leteprinim potassium) to rats immediately after acute
spinal cord injury (SCI), improves functional outcome. The effects of potential new agents are often compared to
methylprednisolone (MPSS). We evaluated the effects of
AIT-082 and MPSS, separately and in combination, on the functional and morphological outcome of acute SCI in adult rats. After standardized T11-12
spinal cord compression rats were given intraperitoneally one of the following: vehicle (saline); MPSS (30 mg/kg or 60 mg/kg
body weight, first dose 15 min after crush);
AIT-082 (60 mg/kg
body weight daily, first dose 15 min after crush); or
AIT-082 plus MPSS. After 1, 3, or 21 days, the rats were perfused for histological analysis.
AIT-082 administrations significantly reduced locomotor impairment from 121 days post-operatively. At 1 and 3 days post injury, AIT-082-treatment reduced tissue swelling, tissue loss and
astrogliosis at the injured cords but did not alter the extent of
hemorrhage and the number of macrophages and/or microglia. MPSS reduced
hemorrhage and the number of macrophages and/or microglia, but did not alter
astrogliosis. At 21 days, either
AIT-082 or MPSS administration improved function and morphology similarly (less tissue loss and
astrogliosis). In contrast, administration of
AIT-082 and MPSS together abolished the beneficial effects observed when either
drug was given individually. These results suggest that MPSS and
AIT-082 may exert their beneficial effects through different and potentially antagonistic pathways.