Effects of irisin hormone on motor and sensory functions in a thoracic spinal cord injury model

Spinal cord injury (SCI) is a neurological condition that affects millions of people worldwide, is characterized by motor and sensory impairments, neuropathic pain problems, and seriously affects the quality of life. Exercise is an effective rehabilitation method in recovery after SCI. Irisin is a myokine that is induced by exercise and has beneficial effects in metabolic diseases, and its role in the recovery of motor and sensory losses after SCI is unknown. In this thesis, the effects of irisin on motor and sensory function losses after SCI, its role in changes at the immunohistochemical level, and its neuroprotective and neurogenerative properties were investigated. In the study, male Sprague Dawley rats were divided into four groups: control, sham, SCI+Deionized water (Di) and SCI+Irisin. Irisin or Di water was administered intraperitoneally at a dose of 100 ng/kg for 6 weeks to the animals, which were modeled by clip compression method at T10 level. Motor functions were evaluated with Basso, Beattie, Bresnahan (BBB) locomotor test and inclined plane tests; neuropathic pain was evaluated with mechanical allodynia, hot plate and cold plate tests. At the end of the experiment, the animals were decapitated and spinal cord tissues were taken and the neuroprotective and neurogenerative effects of irisin were analyzed by immunohistochemical method using the biomarkers Insulin-Like Growth Factor-1 (IGF-1), Brain Derived Neurotrophic Factor (BDNF), Glial Fibrillary Acidic Protein (GFAP), Nerve Growth Factor (NGF), Neurotrophin-3 (NT-3) and Synapsin-1. In functional evaluations, statistically significant differences were detected in BBB scores and inclined plane test results between the groups in all weeks after the model was created. A significant improvement was shown in BBB scores and inclined plane values in the irisin group. While latency periods after SCI decreased significantly in hot plate and cold plate tests, irisin partially prevented this decrease. No significant difference was observed between the groups in the mechanical allodynia test. It was determined that IGF-1 and NT-3 immunoreactivity levels were statistically significantly decreased in the injury groups compared to the control and sham groups. Irisin application partially corrected the decrease in these neurotrophic factors, but the changes did not reach statistical significance. BDNF immunoreactivity in the SCI+Di group was significantly decreased compared to all other groups. Although irisin applied after SCI brought BDNF immunoexpression closer to the control group, this increase was not found to be significant. NGF immunoreactivity was also found to be significantly decreased in the model groups compared to the control and sham groups. No significant difference was detected between the groups in terms of the levels of Synapsin-1, an indicator of synaptic plasticity, and GFAP, an astrocyte activation marker. This study demonstrates that irisin, an exercise-induced adipo-myokine, has the potential to improve motor and sensory functions, alleviate neuronal damage, and prevent apoptosis after SCI. Accordingly, irisin application is considered a promising agent that can contribute to the development of new therapeutic approaches for the treatment of neurological disorders with its neuroprotective effects.