Review
Multidisciplinary Sciences
Erika Wakayama, Taiki Kuzu, Keisuke Tachibana, Ryuichi Hirayama, Yoshiaki Okada, Masuo Kondoh
Summary: The blood-brain barrier poses a challenge to drug delivery to the central nervous system. Among the components of the tight junctions in the blood-brain barrier, claudin-5 has been studied extensively as a target for enhancing drug permeation into the brain. However, sustained knockdown of claudin-5 is lethal in mice and administration of an anti-claudin-5 antibody can cause convulsions in nonhuman primates.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Article
Biology
Esther Sasson, Shira Anzi, Batia Bell, Oren Yakovian, Meshi Zorsky, Urban Deutsch, Britta Engelhardt, Eilon Sherman, Gad Vatine, Ron Dzikowski, Ayal Ben-Zvi
Summary: Through super-resolution microscopy, new structural and functional properties of BBB TJs were revealed, showing a compacting arrangement of claudin-5 proteins during mouse development. The clustering of ZO1 was found to be independent of claudin-5 in vivo, and contrary to previous knowledge, total levels of claudin-5 were inversely correlated with TJ functionality in the developmental context.
Article
Engineering, Environmental
Zengjin Wang, Congcong Zhang, Fengyan Huang, Xiaojing Liu, Zhiping Wang, Bing Yan
Summary: Ingestion of nanoparticles during pregnancy can be dangerous to fetal brain development, especially in early pregnancy. Experimental results show that nanoparticles can cross multiple biological barriers, and the toxicity to the fetus depends on the stages of pregnancy and fetal development.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Immunology
Xin Wang, Jia-ying Yu, Yan Sun, Heng Wang, Hu Shan, Shubai Wang
Summary: Baicalin, a bioactive extract from Scutellaria Baicalensis Georgi, has anti-inflammatory and anti-oxidative functions, and its preventive protection can improve cell apoptosis and Fluorescein sodium infiltration in the brain tissue. Baicalin can also inhibit pro-inflammatory cytokines production, up-regulate Claudin-5 and ZO-1 protein expression, reduce ROS and MDA production, promote SOD production, and activate Nrf2-mediated antioxidant stress pathway to protect blood-brain barrier damage.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Xiaoqing Li, Vamsidhara Vemireddy, Qi Cai, Hejian Xiong, Peiyuan Kang, Xiuying Li, Monica Giannotta, Heather N. Hayenga, Edward Pan, Shashank R. Sirsi, Celine Mateo, David Kleinfeld, Chris Greene, Matthew Campbell, Elisabetta Dejana, Robert Bachoo, Zhenpeng Qin
Summary: The study successfully synthesized gold nanoparticles for increasing blood-brain barrier permeability, demonstrating that transcranial picosecond laser stimulation can regulate BBB permeability, enabling drug delivery without disrupting the structure of the neurovascular unit.
Review
Medicine, Research & Experimental
Xiangyi Zheng, Beida Ren, Ying Gao
Summary: Tight junctions (TJs) play a crucial role in intercellular connections. Abnormal expression of TJ-related proteins can lead to TJ destruction, structural damage, and dysfunction of endothelial and epithelial cells, which are associated with the occurrence and progression of various diseases. The blood-brain barrier (BBB) damage and dysfunction are significant pathological features of stroke, and TJs have a direct impact on BBB integrity. This article discusses the structure, function, regulatory mechanisms, and therapeutic potential of BBB TJs in ischemic stroke.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Andrea E. Toth, Hans C. Helms, Andras Harazin, Kasper B. Johnsen, Charlotte Goldeman, Annette Burkhart, Maj S. Thomsen, Paul J. Kempen, Adrian Klepe, Dora V. Lipka, Peter L. Moller, Thomas L. Andresen, Mette Nyegaard, Torben Moos, Birger Brodin, Morten S. Nielsen
Summary: Sortilin acts as a crucial regulatory protein for maintaining the tightness of the blood-brain barrier (BBB). Lack of sortilin results in BBB leakage, potentially due to alterations in signalling pathways, leading to compromised connections between brain endothelial cells.
Article
Biochemistry & Molecular Biology
Jong-Chan Ahn, Su Jung Hwang, Hyo-Jong Lee, Kyu-Won Kim
Summary: The study showed that claudin-5a is crucial for establishing and maintaining the blood-neural barrier during zebrafish development. Knockdown of claudin-5a resulted in selective leakage through the BBB, decreased expression of glucose transporter 1 in cerebral microvessels, and leakiness in the blood-cerebrospinal fluid barrier, indicating overall abnormal development of the blood-neural barriers.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2021)
Article
Neurosciences
Chelsea M. Phillips, Allison M. Johnson, Svetlana M. Stamatovic, Richard F. Keep, Anuska V. Andjelkovic
Summary: This study reveals that the absence of CCM3 leads to structural defects in the brain endothelial barrier, increasing the risk of vascular leakage. The upregulation of GJA1-20 k is found to disrupt the balance between gap junctions and tight junctions, destabilizing the tight junction complex and increasing brain endothelial barrier permeability.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biotechnology & Applied Microbiology
Xiang Li, Xiaoyan Tian
Summary: Pimavanserin effectively reverses neurological deficits, brain edema, increased inflammatory response, BBB permeability, and downregulation of Claudin 5 caused by cerebral ischemia injury. Its protective effects are mediated by regulating BBB integrity in a KLF6-dependent manner.
Article
Clinical Neurology
Yosuke Hashimoto, Karine Poirier, Nathalie Boddaert, Laurence Hubert, Melodie Aubart, Anna Kaminska, Marianne Alison, Isabelle Desguerre, Arnold Munnich, Matthew Campbell
Summary: This study reports a novel mutation in the CLDN5 gene associated with alternating hemiplegia with microcephaly. The mutation leads to the conversion of the blood-brain barrier into an anion-selective channel, indicating that CLDN5 associated alternating hemiplegia is a channelopathy.
Article
Cell Biology
Jacopo Junio Valerio Branca, Matteo Boninsegna, Gabriele Morucci, Donatello Carrino, Claudio Nicoletti, Ferdinando Paternostro, Massimo Gulisano, Leonardo Bocchi, Alessandra Pacini
Summary: With the advancements in medicine, the increase in human life expectancy has led to a higher incidence of age-associated pathologies. Among these disorders, neurodegenerative diseases have a significant impact and the protective blood-brain barrier (BBB) presents a challenge for drug delivery. However, targeting the BBB by ultrasound (US) has been shown to transiently increase its permeability and allow the delivery of therapeutics to the brain. In this study, the effects of US treatment on the BBB were investigated using cell viability assays, Western blotting analysis, oxidative stress marker evaluation, and cytological and immunofluorescence staining. The results showed that US treatment caused no toxicity to the endothelial cells and induced a transient increase in intercellular spaces, mainly due to altered distribution of the tight junction protein ZO-1. These findings suggest that US treatment could be a potential strategy for improving drug delivery to the brain.
Review
Biochemistry & Molecular Biology
Bo Zhao, Qiyang Yin, Yuxiang Fei, Jianping Zhu, Yanying Qiu, Weirong Fang, Yunman Li
Summary: This review summarizes the role of tight junction protein families in inflammation in the central nervous system and provides a comprehensive understanding of the mechanisms by which inflammation disrupts the blood-brain barrier through the degradation of tight junction proteins.
ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sithara Thomas, Jayanarayanan Sadanandan, Spiros L. Blackburn, Devin W. McBride, Ari Dienel, Sungha Hong, Hussein A. Zeineddine, Peeyush Kumar Thankamani
Summary: Brain vascular staining is crucial for understanding cerebrovascular disorders. The standard fixation technique, 4% paraformaldehyde, produces inconsistent staining results due to antigen masking. Our study demonstrates that a new fixation protocol using 3% glyoxal improves the staining of brain vasculature.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Jun Chen, Xue Wang, Jian Hu, Jingting Du, Confidence Dordoe, Qiulin Zhou, Wenting Huang, Ruili Guo, Fanyi Han, Kaiming Guo, Shasha Ye, Li Lin, Xiaokun Li
Summary: FGF20 reduces neurofunctional deficits, brain edema, and neuroinflammation in TBI mouse model and in vitro experiments, protects BBB integrity by upregulating junction protein expression, and inhibiting the inflammatory response through specific signaling pathways.
FRONTIERS IN PHARMACOLOGY
(2021)
