The Bıochemıcal, Hıstopathologıcal And Clınıcal Comparıson Of The Neuroprotectıve Effects Of Subcutaneous Adalımumab And Intravenous Methylprednısolone In An Experımental Compressıve Spınal Cord Trauma Model

INTRODUCTIONSpinal cord injury (SCI) is a significant clinical problem that can lead to persistent neurological deficits and secondary complications and decrease the quality of life. Primary mechanical damage cause by trauma to the spinal cord is followed by secondary damage with increased calcium and the release of excitatory amino acids, free oxygen radicals and many chemical substances such as TNF-á, IL–1, IL–6 and IL–8 (19,20,72). Medical treatment for traumatic spinal cord injury aims to prevent secondary damage (18,21,34,71).Models such as laceration (56), impact (57),clip compression (60) and dislocation (22) have previously been used to create experimental spinal cord injury.The neuroprotective effect of many pharmacological agents such as methylprednisolone, melatonin, erythropoietin, magnesium, mexiletine, naloxone, infliximab, clotrimazole, lamotrigine and hyperbaric oxygen in experimental spinal cord injury has been studied (4,13,33,37,38,39,40,47,75,76,80,82).Among these substances, only methylprednisolone has entered clinical use (32) and it is the only agent proven to have positive effects after spinal cord injury. However, despite the beneficial effect on parenchymal damage, it has been shown not to provide a significant functional improvement (62).TNF-α and pro-inflammatory cytokines such as IL-1β and IL-6 have been found to increase within hours after spinal cord injury and recent studies have revealed that these cytokines that increase in serum are directly related to persistent motor dysfunction and histopathological damage (25,31,68).Malondialdehyde (MDA) that has an aldehyde structure appears after breaking of the carbon bonds during lipid peroxidation. Malondialdehyde is a final product in lipid peroxidation and MDA levels are used as an indicator of the level of oxidative damage. MDA plasma and tissue levels are measured as an indicator of free radicals (55). Adalimumab (HumiraR) is a human monoclonal TNF-α antibody drug and blocks the effects of TNF-α. It is used successfully at a dose of 40 mg/kg subcutaneously every 2 weeks in the treatment of disorders such as Crohn's disease, ulcerative colitis, psoriasis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis (14,35,42,43,59,65).This study was conducted to evaluate whether adalimumab, an agent commonly used in rheumatology and gastroenterology disorders, has neuroprotective effects in an experimental compressive spinal cord injury model by assessment of histopathological changes in the traumatized tissue; serum MDA, TNF-α, IL-1β and IL–6 measurements; and clinical use of theInclined plane test and Modified Tarlov’s Grading Scale. We then compared the results with those of methylprednisolone, another commonly used agent. This is the first study to investigate the neuroprotective effects of adalimumab in experimental spinal cord injury.