The Role of Tasimelteon in Modulating Cardiac Injury Following Traumatic Brain Injury: A Focus on Bax/Bcl-2, SIRT1/p53 Signaling, and Inflammatory Cytokine Pathways

Abstract

Aim: This study explores the cardioprotective effects of Tasimelteon (TASI), a selective melatonin receptor agonist, following traumatic brain injury (TBI). TBI triggers systemic inflammation, contributing to secondary cardiac injury and increased morbidity. While TASI shows neuroprotective properties, its potential to protect the heart after TBI remains unknown. Methods: Four groups were created from thirty-two adult male rats: Trauma, Trauma + TASI (1 mg/kg), Trauma + TASI (10 mg/kg), and Sham. Heart tissue was taken for genetic, immunohistochemical, and histopathological examinations. Histopathology assessed hyperemia, hemorrhage, inflammation, and necrosis. Immunohistochemistry measured β-tubulin, IL-1, and IL-6 expression, while RT-qPCR analyzed SIRT1, p53, BAX, and BCL-2 mRNA levels. Results: The Trauma group displayed symptoms of myocardial damage, such as hyperemia, bleeding, and disturbed cell architectures, but the Sham group's histopathological analysis indicated normal myocardial tissue. TASI treatments improved these findings, with TASI-10 being more effective. Immunohistochemistry showed minimal expression of β-tubulin, IL-1, and IL-6 in the Sham group, but significant upregulation in the Trauma group, indicating inflammation. Both TASI treatments reduced these markers, with TASI-10 showing the greatest reduction. According to gene expression study, trauma reduced anti-apoptotic genes (Sirt-1, Bcl-2) and elevated pro-apoptotic genes (Bax, p53). Gene expression was slightly restored by TASI-1, but TASI-10 significantly improved all four genes. Conclusion: TASI treatment, particularly at a 10 mg dose, effectively ameliorates myocardial injury caused by Trauma, with improvements observed at the histological, molecular, and gene expression levels. This suggests that TASI may hold potential as a therapeutic agent for myocardial protection.

Keywords

• Apoptosis
• Cardioprotective
• Inflammation
• Tasimelteon
• Traumatic Brain Injury

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