{"title":"miR-204-5p的下调通过Wnt2/Ephrin-A2/EphA7通路促进新生大鼠缺氧缺血性脑损伤后神经再生和功能恢复。","authors":"Mengzao He, Yejun Zhao, Jinping Jiang, Ling Fan, Weinong Mo, Qiang Yao, Yanwen Wang, Minzhi He, Fangfang Shen","doi":"10.1097/WNR.0000000000002184","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Neonatal hypoxic-ischemic brain damage (HIBD) can cause short- and long-term neurological damage. MicroRNA (miR)-204-5p is closely associated with nerve injury caused by brain injury, but its mechanism in HIBD is not very clear.</p><p><strong>Methods: </strong>The neonatal rat's HIBD model was constructed by the modified Rice-Vannucci method, and the expression of miR-204-5p was detected. After overexpression or knockdown of miR-204-5p and application of Wnt2 activator HLY78, the histopathological changes and neuronal degeneration in the hippocampal CA1 region were observed with pathological staining. The neurological function was assessed with a diving platform test and elevated plus-maze test. Nerve regeneration-related protein and Wnt2/Ephrin-A2 (Eph receptor-interacting proteins)/EphA7 (erythropoi-etin-producing hepatomocellular receptor) signaling pathway protein levels were detected by immunohistochemistry and western blot, respectively.</p><p><strong>Results: </strong>miR-204-5p was highly expressed in HIBD. When miR-204-5p was knocked down, the morphology of nerve cells and Nissl bodies was notably improved, Fluoro-Jade C and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells number was significantly reduced. The levels of brain-derived neurotrophic factor and growth-associated protein 43 were significantly increased, and the behavioral indicators of the diving platform and elevated plus-maze test were significantly alleviated. The nerve injury was repaired, and the Wnt2/Ephrin-A2/EphA7 signaling pathway protein was notably elevated. The overexpressed miR-204-5p aggravated the nerve injury in HIBD rats. After the application of HLY78, the neuropathological damage of HIBD rats was further repaired, and the nerve regeneration and function were also significantly improved.</p><p><strong>Conclusion: </strong>Knockdown of miR-204-5p can improve HIBD in neonatal rats by activating the Wnt2/Ephrin-A2/EphA7 signaling pathway to encourage nerve regeneration and functional recovery.</p>","PeriodicalId":19213,"journal":{"name":"Neuroreport","volume":" ","pages":"609-622"},"PeriodicalIF":1.6000,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188836/pdf/","citationCount":"0","resultStr":"{\"title\":\"Knockdown of miR-204-5p promotes nerve regeneration and functional recovery after hypoxic-ischemic brain damage in neonatal rats via the Wnt2/Ephrin-A2/EphA7 pathway.\",\"authors\":\"Mengzao He, Yejun Zhao, Jinping Jiang, Ling Fan, Weinong Mo, Qiang Yao, Yanwen Wang, Minzhi He, Fangfang Shen\",\"doi\":\"10.1097/WNR.0000000000002184\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Neonatal hypoxic-ischemic brain damage (HIBD) can cause short- and long-term neurological damage. MicroRNA (miR)-204-5p is closely associated with nerve injury caused by brain injury, but its mechanism in HIBD is not very clear.</p><p><strong>Methods: </strong>The neonatal rat's HIBD model was constructed by the modified Rice-Vannucci method, and the expression of miR-204-5p was detected. After overexpression or knockdown of miR-204-5p and application of Wnt2 activator HLY78, the histopathological changes and neuronal degeneration in the hippocampal CA1 region were observed with pathological staining. The neurological function was assessed with a diving platform test and elevated plus-maze test. Nerve regeneration-related protein and Wnt2/Ephrin-A2 (Eph receptor-interacting proteins)/EphA7 (erythropoi-etin-producing hepatomocellular receptor) signaling pathway protein levels were detected by immunohistochemistry and western blot, respectively.</p><p><strong>Results: </strong>miR-204-5p was highly expressed in HIBD. When miR-204-5p was knocked down, the morphology of nerve cells and Nissl bodies was notably improved, Fluoro-Jade C and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells number was significantly reduced. The levels of brain-derived neurotrophic factor and growth-associated protein 43 were significantly increased, and the behavioral indicators of the diving platform and elevated plus-maze test were significantly alleviated. The nerve injury was repaired, and the Wnt2/Ephrin-A2/EphA7 signaling pathway protein was notably elevated. The overexpressed miR-204-5p aggravated the nerve injury in HIBD rats. After the application of HLY78, the neuropathological damage of HIBD rats was further repaired, and the nerve regeneration and function were also significantly improved.</p><p><strong>Conclusion: </strong>Knockdown of miR-204-5p can improve HIBD in neonatal rats by activating the Wnt2/Ephrin-A2/EphA7 signaling pathway to encourage nerve regeneration and functional recovery.</p>\",\"PeriodicalId\":19213,\"journal\":{\"name\":\"Neuroreport\",\"volume\":\" \",\"pages\":\"609-622\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-08-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188836/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neuroreport\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/WNR.0000000000002184\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/6/13 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuroreport","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/WNR.0000000000002184","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/13 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Knockdown of miR-204-5p promotes nerve regeneration and functional recovery after hypoxic-ischemic brain damage in neonatal rats via the Wnt2/Ephrin-A2/EphA7 pathway.
Objective: Neonatal hypoxic-ischemic brain damage (HIBD) can cause short- and long-term neurological damage. MicroRNA (miR)-204-5p is closely associated with nerve injury caused by brain injury, but its mechanism in HIBD is not very clear.
Methods: The neonatal rat's HIBD model was constructed by the modified Rice-Vannucci method, and the expression of miR-204-5p was detected. After overexpression or knockdown of miR-204-5p and application of Wnt2 activator HLY78, the histopathological changes and neuronal degeneration in the hippocampal CA1 region were observed with pathological staining. The neurological function was assessed with a diving platform test and elevated plus-maze test. Nerve regeneration-related protein and Wnt2/Ephrin-A2 (Eph receptor-interacting proteins)/EphA7 (erythropoi-etin-producing hepatomocellular receptor) signaling pathway protein levels were detected by immunohistochemistry and western blot, respectively.
Results: miR-204-5p was highly expressed in HIBD. When miR-204-5p was knocked down, the morphology of nerve cells and Nissl bodies was notably improved, Fluoro-Jade C and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells number was significantly reduced. The levels of brain-derived neurotrophic factor and growth-associated protein 43 were significantly increased, and the behavioral indicators of the diving platform and elevated plus-maze test were significantly alleviated. The nerve injury was repaired, and the Wnt2/Ephrin-A2/EphA7 signaling pathway protein was notably elevated. The overexpressed miR-204-5p aggravated the nerve injury in HIBD rats. After the application of HLY78, the neuropathological damage of HIBD rats was further repaired, and the nerve regeneration and function were also significantly improved.
Conclusion: Knockdown of miR-204-5p can improve HIBD in neonatal rats by activating the Wnt2/Ephrin-A2/EphA7 signaling pathway to encourage nerve regeneration and functional recovery.
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NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.
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