Methothrexate attenuates early neutrophil infiltration and the associated lipid peroxidation in the injured spinal cord but does not induce neurotoxicity in the uninjured spinal cord in rats

摘要

Backround: The goal of most acute therapies for spinal cord injury (SCI) in humans include attenuation of the early inflammatory response and may limit the extent of tissue injury and the consequent disability. Objective: The purpose of this study was to investigate the early effects of methothrexate (MTX) treatment on myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, and ultrastructural findings in the injured and uninjured spinal cords of rats. The effects of MTX treatment were also compared with methylprednisolone sodium succinate (MPSS) treatment. Methods: Winstar rats were divided into seven groups: control; trauma alone (50 g/cm weight drop trauma); SCI + MPSS (30 mg/kg); SCI + low-dose (0.5 mg/kg) MTX (LDMTX); SCI + higher-dose (1 mg/kg) MTX (HDMTX); non-trauma + LDMTX; non-trauma + HDMTX. Results: Administration of MTX and MPSS treatments significantly decreased MPO activity (p∈<∈0.05) and MDA level (p∈<∈0.05) in the first 24 h. The MTX treatments, particularly HDMTX, were more effective than MPSS in reducing MPO activity, and MTX treatments were also more effective than MPSS in reducing MDA level (p∈<∈0.05). The MTX treatment was more protective on large- and medium-diameter myelinated axons in minimizing ultrastructural changes in the spinal-cord-injured rats, but did not induce neurotoxicity in normal spinal cord. ConclusIon: The results of this study indicate that MTX treatment has a benefical effect by reducing early neutrophil infiltration and the associated lipid peroxidation, and has significantly protective effects on the injured spinal cord tissue in the first 24 h after SCI. Given the anti-inflammatory properties of MTX, a single dose of MTX a week is used for non-neoplastic disease in humans, and MTX may have a benificial role in the immediate management of acute SCI.