EXPERIMENTAL RESEARCH 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 Ahmet Metin Şanlı & Gökhan Serbes & Mustafa F. Sargon & Murat Çalışkan & Kamer Kılınç & Hüsamettin Bulut & Zeki Şekerci Received: 14 October 2011 / Accepted: 3 February 2012 / Published online: 22 February 2012 # Springer-Verlag 2012 Abstract 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 myeloper- oxidase (MPO) activity, malondialdehyde (MDA) level, and ultrastructural findings in the injured and uninjured spinal cords of rats. The effects of MTX treatment were also com- pared with methylprednisolone sodium succinate (MPSS) treatment. Methods Winstar rats were divided into seven groups: con- trol; 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 sig- nificantly 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 treat- ment 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. Conclusıon The results of this study indicate that MTX treat- ment has a benefical effect by reducing early neutrophil infil- tration 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 prop- erties 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. Keywords Inflammation . Lipid peroxidation . Methotrexate . Methylprednisolone sodium succinate . Neuroprotection . Spinal cord injury Introductıon In spinal cord injury (SCI), spinal cord tissue is damaged by both a primary and secondary injury mechanism. The A. M. Şanlı : G. Serbes : H. Bulut : Z. Şekerci 1st Neurosurgery Clinic, Diskapi Yildirim Beyazit Education and Research Hospital, Ministry of Health, 06610 Ankara, Turkey M. F. Sargon Department of Anatomy, Faculty of Medicine, Hacettepe University, Ankara, Turkey M. Çalışkan Department of Surgery, Faculty of Veterinary Medicine, Ankara University, 06615 Ankara, Turkey K. Kılınç Department of Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey A. M. Şanlı (*) Mebusevleri Mah. Ayten Sokak, No: 6/7 Tandoğan, Ankara 06580, Turkey e-mail: ahmetmetinsanli@hotmail.com Acta Neurochir (2012) 154:1045–1054 DOI 10.1007/s00701-012-1302-8