Evaluation of therapeutic and preservative effects of etanercept-methotrexate combination in experimental rat spinal injury model

Introduction: Traumatic spinal injury (TSI) is defined as a sudden, devastating, debilitating event which causes highly valued personal and social costs; and physiological, sociological problems. Even though advancements in medical care have improved rates of morbidity and mortality, progress in pharmacotherapy which has been developed to stimulate regeneration and restrict neuronal damage, is still limited. One reason for treatment modalities, which have been successful in preclinical trials, to end up with limited results in clinical studies, is the complexity of the secondary degenerative response which has been triggered by the primary mechanical injury. Most of the mono-therapies affect, only one stage of the secondary injury mechanism; whereas a successful treatment should be effective in many stages. Therefore combined therapy practices are being prioritized in clinical and experimental trials. This study is designed to understand if Etanercept+Methotrexate combination in TSI has any synergistic effects or not. Methods: In this study with the use of histological (Luxol fast hematoxylin-eosin and TUNEL dying) and neurological examination (Inclined plane and motor scoring) methods; preservative and therapeutic efficacies of Etanercept, Methotrexate and Etanercept+Methotrexate combination in secondary injury are being investigated on spinal injury models which have been created by clip compression technique. 30 Sprague Dawley breed mature female rats were exploited in this study. Following the anesthesia, with a skin incision through the space between T7-T9 (thoracal vertebras), paravertebral muscles were dissected; and five groups, 6 rats in each, were comprised: group 1 (the control group), group 2 (laminectomy + cord compression), group 3 (laminectomy + cord compression + Etanercept), group 4 (laminectomy + cord compression + Methotrexate) and group 5 (laminectomy + cord compression + Etanercept + Methotrexate). Subjects were evaluated at days 1, 3, 5 and 10 for their inclined plane and motor scores. All were sacrificed at day 10 for the histopathological examination. Findings: Regarding the clinical findings, in each mono-therapy group with respect to trauma group, a significant recovery, and in correspondence to that a significant reduction of necrosis and apoptosis rates in histological results were found. When two mono-therapy groups were compared, there was no significant difference in clinical and histological manners, whereas a partial difference was observed in favor of Etanercept. In comparison of combination therapy group verses trauma group, a significant difference in the favor of combination therapy -regarding the clinical findings and apoptosis- was found. When compared with the mono-therapies, combination therapy is found to be significantly superior to mono-therapy groups in histological aspect (necrosis and apoptosis reduction), whereas this superiority cannot be kept in clinical sense. Results: Neither the number of subjects in our trial nor the quantity of studies in the literature is efficient enough to clearly manifest the effects of Methotrexate + Etanercept combination in TSI. Therefore more experimental and clinical studies are needed to be accomplished.