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Neuroprotective role of remote ischemic post-conditioning in radiotherapy-induced cognitive decline: Modulating hippocampal phospho-tau and autophagy via Nrf2-ARE pathway
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F. Yang   , W. Qi , F. Zhou , S. Li , M. Zhang , Y. Zong , H. Yang , X. Hu |
| School of Nursing, Qingdao Binhai University, Qingdao, Shandong, China; Department of Pathology, Chengdu Medical College, Sichuan, 610500, China; Philippine Women's University, 1743 Taft Avenue, Malate, Manila 1004 , 793219993@qq.com |
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Abstract: (86 Views) |
Background: Cranial radiotherapy (RT), while critical for treating brain tumors, often leads to delayed cognitive dysfunction due to neuronal damage and Tau protein accumulation. Remote ischemic post-conditioning (RIPC) has emerged as a potential strategy to mitigate RT-induced neurotoxicity. This study explores the neuroprotective role of RIPC in modulating hippocampal autophagy and phospho-Tau (P-Tau) expression through the Nrf2-antioxidant response element (ARE) signaling pathway following cranial irradiation. Materials and Methods: Male Sprague-Dawley rats were subjected to focal cranial RT to induce radiation-associated hippocampal injury. A subgroup received RIPC through intermittent limb ischemia. Behavioral evaluations, including Morris water maze, elevated plus maze, and novel object recognition tests, were conducted at weeks 4 and 8 post-irradiation. Hippocampal expression levels of Nrf2, HO-1, SOD2, Tau, and P-Tau were assessed via qPCR and ELISA. Immunohistochemistry and immunofluorescence were employed to localize and quantify neuronal changes and autophagy markers. Results: Rats receiving RIPC demonstrated significant improvements in memory and spatial learning compared to non-conditioned controls. RIPC upregulated hippocampal Nrf2, HO-1, and SOD2, while decreasing Tau and P-Tau accumulation. Additionally, increased neuronal autophagy and reduced oxidative stress were observed, correlating with better cognitive outcomes. Conclusion: RIPC exerts neuroprotective effects in a RT-induced brain injury model by activating the Nrf2-ARE pathway, promoting autophagy, and reducing Tau pathology. These findings support the therapeutic potential of RIPC as an adjunct to RT for preserving cognitive function in cancer patients. |
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| Keywords: Radiotherapy, cognitive dysfunction, ischemic preconditioning, hippocampus, Tau proteins, autophagy. |
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Full-Text [PDF 1464 kb]
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Type of Study: Original Research |
Subject:
Radiation Biology
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