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A New Approach for Exploring Reperfusion Brain Damage in Hypoxic Ischemic Encephalopathy

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Abstract

Reperfusion is an essential pathological stage in hypoxic ischemic encephalopathy (HIE). Although the Rice-Vannucci model is widely used in HIE research, it remains difficult to replicate HIE-related reperfusion brain injury. The purpose of this study is to establish a rat model of hypoxia ischemia reperfusion brain damage (HIRBD) using a common carotid artery (CCA) muscle bridge in order to investigate the mechanisms of cerebral resistance to hypoxic-ischemic and reperfusion brain damage. Random assignment of Sprague–Dawley (SD) rats to the Sham, HIRBD, and Rice-Vannucci groups. Changes in body weight, mortality rate, spontaneous alternation behavior test (SAB test), and dynamic changes in cerebral blood flow (CBF) were detected. The damaged cerebral cortices were extracted for morphological comparison, transcriptomic analysis, and quantitative real-time PCR. Harvesting the hippocampus for transmission electron microscopy (TEM) detection. As a result, CCA muscle bridge could effectively block CBF, which recovered after the muscle bridge detachment. Pathological comparison, the SAB test, and TEM analysis revealed that brain damage in Rice-Vannucci was more severe than HIRBD. Gpx1, S100a6, Cldn5, Esr1, and Gfap were highly expressed in both HIRBD and Rice-Vannucci. In conclusion, the CCA muscle bridge-established HIRBD model could be used as an innovative and dependable model to simulate pathological process of HIRBD.

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Data Availability

Data are available on reasonable request. All raw data used in this manuscript are available on reasonable request.

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Funding

This research was supported by the National Natural Science Foundation of China (No. 82271747) and the Natural Science Foundation of Zhejiang Province (No. LY23H040004).

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Authors and Affiliations

  1. Department of Pediatrics, the Second School of Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Tianlei Zhang, Mengdie Jiao, Jianghu Zhu, Xiaoling Guo & Zhenlang Lin

  2. Second Clinical Medical College, Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Zhiwei Zhang, Jiayi Geng, Kexin Lin, Xinru Lin & Zhenlang Lin

  3. Key Laboratory of Children Genitourinary Diseases of Wenzhou, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Jianghu Zhu & Zhenlang Lin

  4. Key Laboratory of Perinatal Medicine of Wenzhou, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Xiaoling Guo

  5. Basic Medical Research Center, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China

    Xiaoling Guo

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  1. Tianlei Zhang
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  2. Zhiwei Zhang
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Contributions

Z.L. is the principal investigator and designed the study. T.Z. and Z.Z. contributed to the study design, experiment implementation and manuscript draft. J.G., K.L., M.J., and X. L. summarized and analyzed the experimental data. X.G. and J.Z. revised the manuscript and polished the language. The author(s) read and approved the final manuscript. T.Z. is responsible for the overall content as the guarantor.

Corresponding authors

Correspondence to Jianghu Zhu, Xiaoling Guo or Zhenlang Lin.

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All animal experiments were performed according to the Institutional Animal Care and Use Committee (IACUC). The procedures were conducted according to the National Institutes of Health’s Guide for the Care and the Use of Laboratory Animals and the Animal Research: Reporting In Vivo Experiments (ARRIVE) guidelines, and all animals were approved by the Animal Experimentation Ethics Committee of Wenzhou Medical University.

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Tianlei Zhang, Zhiwei Zhang, Jiayi Geng, and Kexin Lin contributed equally to this work.

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Zhang, T., Zhang, Z., Geng, J. et al. A New Approach for Exploring Reperfusion Brain Damage in Hypoxic Ischemic Encephalopathy. Mol Neurobiol 61, 1417–1432 (2024). https://doi.org/10.1007/s12035-023-03645-9

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