International Journal of Radiation Research

en Neuroprotective role of remote ischemic post-conditioning in radiotherapy-induced cognitive decline: Modulating hippocampal phospho-tau and autophagy via Nrf2-ARE pathway Radiation Biology Radiation Biology تحقيق بديع Original Research <div style="text-align: justify;">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.</div> Radiotherapy, cognitive dysfunction, ischemic preconditioning, hippocampus, Tau proteins, autophagy. 1071 1077 http://ijrr.com/browse.php?a_code=A-10-1-1438&slc_lang=en&sid=1 F. Yang 7900319475328460032552 7900319475328460032552 No Qingdao Huanghai University, Qingdao, Shandong, China W. Qi 793219993@qq.com 7900319475328460032553 7900319475328460032553 Yes 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 F. Zhou 7900319475328460032554 7900319475328460032554 No Sichuan Medical College, Nanchong, Sichuan, China S. Li 7900319475328460032555 7900319475328460032555 No Department of Pathology, Chengdu Medical College, Sichuan, China M. Zhang 7900319475328460032556 7900319475328460032556 No Department of Pathology, Chengdu Medical College, Sichuan, China Y. Zong 7900319475328460032557 7900319475328460032557 No Department of Pathology, Chengdu Medical College, Sichuan, China H. Yang 7900319475328460032558 7900319475328460032558 No Department of Pathology, Chengdu Medical College, Sichuan, China X. Hu 7900319475328460032559 7900319475328460032559 No Department of Pathology, Chengdu Medical College, Sichuan, China