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Ischemia Reperfusion Injury Induced Blood Brain Barrier Dysfunction and the Involved Molecular Mechanism

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Abstract

Stroke is characterized by the abrupt failure of blood flow to a specific brain region, resulting in insufficient supply of oxygen and glucose to the ischemic tissues. Timely reperfusion of blood flow can rescue dying tissue but can also lead to secondary damage to both the infarcted tissues and the blood–brain barrier, known as ischemia/reperfusion injury. Both primary and secondary damage result in biphasic opening of the blood–brain barrier, leading to blood–brain barrier dysfunction and vasogenic edema. Importantly, blood–brain barrier dysfunction, inflammation, and microglial activation are critical factors that worsen stroke outcomes. Activated microglia secrete numerous cytokines, chemokines, and inflammatory factors during neuroinflammation, contributing to the second opening of the blood–brain barrier and worsening the outcome of ischemic stroke. TNF-α, IL-1β, IL-6, and other microglia-derived molecules have been shown to be involved in the breakdown of blood–brain barrier. Additionally, other non-microglia-derived molecules such as RNA, HSPs, and transporter proteins also participate in the blood–brain barrier breakdown process after ischemic stroke, either in the primary damage stage directly influencing tight junction proteins and endothelial cells, or in the secondary damage stage participating in the following neuroinflammation. This review summarizes the cellular and molecular components of the blood–brain barrier and concludes the association of microglia-derived and non-microglia-derived molecules with blood–brain barrier dysfunction and its underlying mechanisms.

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Funding

This work was supported by grants from the Natural Science Foundation of Beijing (7214224, M.J), the National Natural Science Foundation of China (81870935, J.W) and the Scientific Research Found of Wuhan University of Technology (40122070, J.W).

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Authors and Affiliations

  1. Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China

    Xi Guo, Ru Liu & Jianping Wu

  2. Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China

    Xi Guo, Ru Liu, Meng Jia, Qun Wang & Jianping Wu

  3. Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, 10070, China

    Xi Guo, Ru Liu, Meng Jia & Jianping Wu

  4. China National Clinical Research Center for Neurological Diseases, Beijing, 10070, China

    Xi Guo, Ru Liu, Meng Jia, Qun Wang & Jianping Wu

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XG conducted the literature review and wrote the initial draft of the manuscript. RL gave important advice on the content of the review. MJ and QW checked the grammar of the review. JW made critical revisions and approved the final version of the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Jianping Wu.

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Guo, X., Liu, R., Jia, M. et al. Ischemia Reperfusion Injury Induced Blood Brain Barrier Dysfunction and the Involved Molecular Mechanism. Neurochem Res 48, 2320–2334 (2023). https://doi.org/10.1007/s11064-023-03923-x

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