Sıçan Spinal Kord Hasarı Modelinde İzoalantolakton’un Nöroinflamasyon Üzerine Etkilerinin İncelenmesi
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Introduction & Objectives: Spinal cord injury (SCI) is a complex and destructive condition that affects many body functions. After the spinal cord trauma, the production of free oxygen radicals in the first 24 hours following the occurrence of damage, disruption of mitochondrial function, and the release of potassium and genetic material from damaged cells (microglia, astrocytes, neurons). Activation of microglial cells in the damaged spinal cord tissue in which trigger the releasing of Pro-inflammatory cytokines such as TNF-α, IL-1β, IL-6, also secreted prostaglandin E2, cyclooxygenase 2 (COX2), Nitro-oxidase (INOS) and activated microglial cells increase the inflammatory cascade. In summary, the pathways of the molecules involved in the inflammation process are activated. Nowadays, the main treatments are about reducing the secondary damage in the process of admission, diagnosis and treatment of these patients. Isoalantolactone (IAL), is a new generation drug with broad biological activity. Studies have shown that isoalantolactone has antibacterial, anti-inflammatory and antiapoptotic effect. In addition, although neuroprotective effect has been demonstrated in rat traumatic brain injury model, there is no study explaining the mechanism of action of this drug in traumatic spinal cord injury. The aim of this study was to investigate the effects of isoalantolactone (IAL) injected intraperitoneally into rats in the spinal cord trauma model on neuroinflammation 24 hours after the trauma and to compare its effects with the commonly used anti-inflammatory drug methylprednisolone. At the end of the 24th hour, post-traumatic neurological evaluation was performed and sacrificed. Then, proinflammatory cytokines such as TNF-α, IL-6 were examined by ELISA method, IL-6, CD3, Micorglia (Iba-1) and Macrophage (F4 / 80) antibodies in spinal cord tissue and compared with control groups. In addition, the subunit of the transcription factor NF-κB, which is responsible for the synthesis of inflammatory mediators, was examined by NF-κB-p65 immunohistochemistry method. This allowed us to evaluate the course of inflammation. Material & Methods: A total of 32 male Wistar rats (n = 8) were used in the study. The groups were divided into four groups as sham group, trauma group, trauma and methylprednisolone group, trauma and isoalantolactone (IAL) group. Spinal trauma model was created by dropping 15 gr free weight from 10 cm height under ketamine / xylazine anesthesia to rats. Half an hour after trauma, a single dose of 20 mg / kg isoalantolactone was administered intraperitoneally, and control groups received intraperitoneal saline or 60 mg / kg methylprednisolone intraperitoneally. Behavioral experiments were performed in all groups before sacrification. At the end of 24th hour, rats were sacrificed and histopathological and immunhistochemical findings of spinal tissues were compared between groups Findings: Isoalantolactone (IAL) reduces inflammation in various ways in traumatic spinal cord injury, one of which is the NF-κB pathway. Using IAL, neurologically significant improvement was achieved in spinal cord injury (p<0.0001). In the IAL group, the total number of NF-κB-labeled cells decreased compared to the other groups (p<0.0001). According to these findings, the neuroinflammatory pathway developed over the NF-κB pathway in the rat spinal cord trauma model was shown. IAL has been shown to inhibit neuroinflammation through the NF-κB pathway. Tissue TNF-α, IL-6 levels were decreased in the IAL group (p<0.002), but not statistically significant (p=0.068). IL-6 and TNF-α secretion were significantly decreased in the IAL group (p=0.002). When microglial and macrophage cells were evaluated with Iba-1 and F4/80, it was seen that microglial and macrophage migration with IAL was significantly less (p=0.0025), (p=0.0363). IAL has been shown to reduce neuroinflammation by suppressing microglia activation after trauma. (p<0.0001), CD3 + T lymphocytes were significantly reduced by IAL (p=0.0084). IAL significantly reduced post-traumatic edema histopathologically. It also reduced the number of neurodegenerative cells compared to the trauma group. Conclusion: In conclusion, Isoalantolactone (IAL) contributed to improvement of neurological functions in moderate spinal cord injury by inhibiting macrophage, microglial activation and NF-κB pathway of the neuroinflammation process. Keywords: Traumatic Spinal Cord injury, methylprednisolone, İsoalantolactone, neuroinflammation, NF-κB .