{"title":"The blood-brain barrier: a help and a hindrance.","authors":"Ruslan Rust, Hao Yin, Beatriz Achón Buil, Abhay Sagare, Kassandra Kisler","doi":"10.1093/brain/awaf068","DOIUrl":null,"url":null,"abstract":"<p><p>The blood-brain barrier (BBB) is a specialized vascular structure that protects the brain microenvironment from toxins and pathogens in the blood. At the same time, the BBB presents a significant challenge for drug development, as it restricts the entry of most therapeutics into the brain. In this review, we first examine recent findings on the molecular and cellular architecture of the BBB, emphasizing the diverse mechanisms that facilitate the transport and exchange of molecules between the blood and the brain. We discuss current knowledge on the heterogeneity of the BBB along the arteriovenous axis and across different brain regions. Then, we explore the molecular and functional changes in the BBB that occur during normal aging, neurodegeneration, and acute brain injuries and how prolonged BBB impairment affects transport mechanisms and disease progression. Additionally, we discuss novel developments in drug delivery strategies to transport small molecules, biologicals or cellular therapeutics across the BBB. Finally, we examine therapeutic opportunities to restore the BBB and discuss future directions in the field.</p>","PeriodicalId":9063,"journal":{"name":"Brain","volume":" ","pages":""},"PeriodicalIF":10.6000,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/brain/awaf068","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The blood-brain barrier (BBB) is a specialized vascular structure that protects the brain microenvironment from toxins and pathogens in the blood. At the same time, the BBB presents a significant challenge for drug development, as it restricts the entry of most therapeutics into the brain. In this review, we first examine recent findings on the molecular and cellular architecture of the BBB, emphasizing the diverse mechanisms that facilitate the transport and exchange of molecules between the blood and the brain. We discuss current knowledge on the heterogeneity of the BBB along the arteriovenous axis and across different brain regions. Then, we explore the molecular and functional changes in the BBB that occur during normal aging, neurodegeneration, and acute brain injuries and how prolonged BBB impairment affects transport mechanisms and disease progression. Additionally, we discuss novel developments in drug delivery strategies to transport small molecules, biologicals or cellular therapeutics across the BBB. Finally, we examine therapeutic opportunities to restore the BBB and discuss future directions in the field.
期刊介绍：
Brain, a journal focused on clinical neurology and translational neuroscience, has been publishing landmark papers since 1878. The journal aims to expand its scope by including studies that shed light on disease mechanisms and conducting innovative clinical trials for brain disorders. With a wide range of topics covered, the Editorial Board represents the international readership and diverse coverage of the journal. Accepted articles are promptly posted online, typically within a few weeks of acceptance. As of 2022, Brain holds an impressive impact factor of 14.5, according to the Journal Citation Reports.
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