Review
Chemistry, Multidisciplinary
Ekta Jagtiani, Mihika Yeolekar, Shivraj Naik, Vandana Patravale
Summary: Understanding the BBB enables the development of new techniques for CNS medication and improvement of existing models. In vitro BBB models have been formed to study the pathology of BBB and its mechanism of action in CNS disorders. The microfluidics-based BBB-on-Chip model has been developed for realistic simulation and drug permeability testing. Evaluating in vitro BBB models is critical for developing CNS treatments with improved BBB penetrability.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Biochemistry & Molecular Biology
Sarah Brandl, Markus Reindl
Summary: The blood-brain barrier, formed by interconnected microvascular endothelial cells, separates the brain from the peripheral circulation. This barrier becomes leaky during neuroinflammation, allowing molecules and cells to enter the brain and potentially cause damage. Animal models may not always represent human pathophysiology accurately, so human models are needed. This review provides an overview of the blood-brain barrier and its role in health and disease, explores in vitro models, and discusses different types of models used in basic research to study neuroinflammatory conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Christopher Pham Pacia, Jinyun Yuan, Yimei Yue, Eric C. Leuthardt, Tammie L. S. Benzinger, Arash Nazeri, Hong Chen
Summary: This study evaluated the feasibility and safety of focused ultrasound-mediated liquid biopsy (sonobiopsy) in detecting brain-derived protein biomarkers in tau protein-related diseases. Sonobiopsy released phosphorylated tau species and neurofilament light chain into the blood circulation, potentially facilitating diagnosis of neurodegenerative disorders.
Review
Pharmacology & Pharmacy
Chloe Whitehouse, Nicola Corbett, Janet Brownlees
Summary: The lack of robust in vitro models to represent complex cellular pathologies underlying neurodegeneration has created a translational gap and bottleneck in new therapeutics development. Recent progress in the development of 3D models of neurodegeneration is reviewed, discussing design benefits, validation techniques, and opportunities for implementation in drug discovery and development, as well as the need for standards.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Neurosciences
Servio H. Ramirez, Tetyana P. Buzhdygan, Jonathan F. Hale, Liang Cheng, Guangming Li, Bryson Hoover-Hankerson, Roshanak Razmpour, Uma Sriram, Lishan Su, Raghava Potula, Allison M. Andrews
Summary: This study demonstrates that HIV infection leads to the release of brain-EC derived extracellular vesicles, causing disruption of the blood-brain barrier. While ART reduces brain-EC EVs, it is unable to completely resolve the increased levels of vesicles detectable in the blood, suggesting potential for EVs as biomarkers for neurocognitive disorders.
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Ye Peng, Shifeng Chu, Yantao Yang, Zhao Zhang, Zongran Pang, Naihong Chen
Summary: Cell cultures are widely used in pharmaceutical, medical, and biological sciences. Neuronal and glial cell models are important tools for researching neurological disorders, with current studies on neuroinflammation contributing to understanding blood-brain barrier damage. Immortalized cell lines of the central nervous system are being used to study anti-inflammatory potential in neurological disorders, with 2D and 3D co-culture models being discussed for their different advantages and limitations.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Neurosciences
Jamie Marino, Monique E. Maubert, Jill M. Lawrence, Brian Wigdahl, Michael R. Nonnemacher
Summary: The blood-brain barrier plays a crucial role in regulating the passage of molecules between the central nervous system and peripheral circulation. Repeat morphine dosing may not significantly affect the integrity of the blood-brain barrier.
Article
Immunology
Julia Mamana, Gabrielle M. Humber, Eric R. Espinal, Soojung Seo, Nadine Vollmuth, Jon Sin, Brandon J. Kim
Summary: Coxsackievirus B3 (CVB3) is a common human pathogen that can cause fatal aseptic meningo-encephalitis, particularly in young children. The mechanisms by which CVB3 gains access to the brain and the virus-host interactions at the blood-brain barrier (BBB) are poorly understood. This study utilized human induced-pluripotent stem cell-derived brain-like endothelial cells (iBECs) to investigate the effects of CVB3 infection on BBB function and overall survival. The results showed that CVB3 infection of iBECs resulted in high extracellular virus release and disruption of transendothelial electrical resistance (TEER) at later infection stages, suggesting potential mechanisms for viral entry and prolonged shedding.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Medicine, General & Internal
Giulia Caligaris, Mattia Trunfio, Valeria Ghisetti, Jessica Cusato, Marco Nigra, Cristiana Atzori, Daniele Imperiale, Stefano Bonora, Giovanni Di Perri, Andrea Calcagno
Summary: Despite the introduction of combination antiretroviral therapy, the prevalence of HIV-associated neurocognitive disorders remains high. Blood-brain barrier impairment is a common issue in people living with HIV and is associated with CSF HIV RNA and neopterin levels. Further studies are needed to explore the influence of sex and treatment on BBB integrity.
Article
Biochemistry & Molecular Biology
Pervaiz Iqra, Zahra Fatema Tuz, Mikelis Constantinos, Al-Ahmad Abraham Jacob
Summary: This study characterized an in vitro model of GLUT1DS using human pluripotent stem cells (iPSCs) generated by CRISPR-Cas9. The results suggest that GLUT1 truncation is detrimental to brain angiogenesis and brain endothelial bioenergetics, but may not be harmful to iBMECs differentiation and barrier function generation.
JOURNAL OF NEUROCHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Dake Qi, Haiyang Lin, Bingying Hu, Yang Wei
Summary: The establishment of in vitro models of the blood-brain barrier (BBB) is important for understanding drug permeability. The hCMEC/D3 cell line shows potential as a standardized BBB model due to its high throughput, reproducibility, homology, and low cost. However, improvements are needed to overcome the low physiological barriers in this model.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Pharmacology & Pharmacy
Karin Danz, Tara Hoecherl, Sascha Lars Wien, Lena Wien, Hagen von Briesen, Sylvia Wagner
Summary: Models of the blood-brain barrier derived from human induced pluripotent stem cells (hiPSs) have shown comparable characteristics to primary cell-based models. Although there were no significant differences in protein expression or permeability, both models deviated from in vivo BBB conditions, specifically regarding the presence or absence of serum proteins. By adjusting the serum distribution, the hiPS-derived BBB model demonstrated improved permeability for hydrophilic and lipophilic compounds. The model was further developed in a microfluidic setup and exhibited comparable permeability coefficients to literature values.
Article
Chemistry, Multidisciplinary
Suyeong Seo, Seung-Yeol Nah, Kangwon Lee, Nakwon Choi, Hong Nam Kim
Summary: The study introduced an engineered 3D human glioblastoma in vitro platform integrated with a tricultured BBB, allowing for mimicking the physiological environment of brain tumors. The platform showed potential for studying the physiology of the BBB and monitoring drug responses based on the interaction between brain tumor cells and the BBB.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Article
Biochemical Research Methods
D. Megarity, R. Vroman, M. Kriek, P. Downey, T. J. Bushell, M. Zagnoni
Summary: Disorders of the central nervous system (CNS) are a global health challenge. Traditional in vitro and animal models have limited validity in simulating the CNS environment. Microfluidic and organ-on-chip technologies offer the opportunity to develop more relevant and complex in vitro models. We introduce a modular platform for creating bespoke culture environments and conducting functional analysis to enhance our understanding of CNS disease mechanisms.
Article
Biochemistry & Molecular Biology
Anett Hudak, Annamaria Letoha, Csaba Vizler, Tamas Letoha
Summary: Early diagnosis of Alzheimer's disease is crucial for preserving patients' health, and the expression of SDC3 in experimental models suggests it could be used as a biomarker for detecting neurodegeneration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Carl I. Webster, Nadia Caram-Salas, Arsalan S. Haqqani, George Thom, Lee Brown, Kerry Rennie, Alvaro Yogi, Willard Costain, Eric Brunette, Danica B. Stanimirovic
Article
Endocrinology & Metabolism
AmanPreet Badhwar, Rebecca Brown, Danica B. Stanimirovic, Arsalan S. Haqqani, Edith Hamel
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2017)
Article
Multidisciplinary Sciences
Maria Ribecco-Lutkiewicz, Caroline Sodja, Julie Haukenfrers, Arsalan S. Haqqani, Dao Ly, Peter Zachar, Ewa Baumann, Marguerite Ball, Jez Huang, Marina Rukhlova, Marzia Martina, Qing Liu, Danica Stanimirovic, Anna Jezierski, Mahmud Bani-Yaghoub
SCIENTIFIC REPORTS
(2018)
Article
Endocrinology & Metabolism
AmanPreet Badhwar, Danica B. Stanimirovic, Edith Hamel, Arsalan S. Haqqani
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2014)
Article
Biochemistry & Molecular Biology
Sabrina Semmler, Myriam Gagne, Pranav Garg, Sarah R. Pickles, Charlotte Baudouin, Emeline Hamon-Keromen, Laurie Destroismaisons, Yousra Khalfallah, Mathilde Chaineau, Elise Caron, Andrew N. Bayne, Jean-Francois Trempe, Neil R. Cashman, Alexandra T. Star, Arsalan S. Haqqani, Thomas M. Durcan, Elizabeth M. Meiering, Janice Robertson, Nathalie Grandvaux, Steven S. Plotkin, Heidi M. McBride, Christine Vande Velde
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Henk van Faassen, Shannon Ryan, Kevin A. Henry, Shalini Raphael, Qingling Yang, Martin A. Rossotti, Eric Brunette, Susan Jiang, Arsalan S. Haqqani, Traian Sulea, C. Roger MacKenzie, Jamshid Tanha, Greg Hussack
Article
Neurosciences
Wandong Zhang, Qing Yan Liu, Arsalan S. Haqqani, Sonia Leclerc, Ziying Liu, Francois Fauteux, Ewa Baumann, Christie E. Delaney, Dao Ly, Alexandra T. Star, Eric Brunette, Caroline Sodja, Melissa Hewitt, Jagdeep K. Sandhu, Danica B. Stanimirovic
FLUIDS AND BARRIERS OF THE CNS
(2020)
Article
Virology
Aline Do Minh, Alexandra T. Star, Jacek Stupak, Kelly M. Fulton, Arsalan S. Haqqani, Jean-Francois Gelinas, Jianjun Li, Susan M. Twine, Amine A. Kamen
Summary: The presence of EVs in lentiviral preparations poses a challenge and requires further understanding and separation strategies. Using mass spectrometry and multi-omics approaches, potential EV markers were successfully identified and the importance of EVs in LV preparations was highlighted.
Article
Endocrinology & Metabolism
Min Su Kang, Monica Shin, Julie Ottoy, Arturo Aliaga Aliaga, Sulantha Mathotaarachchi, Kely Quispialaya, Tharick A. Pascoal, D. Louis Collins, M. Mallar Chakravarty, Axel Mathieu, Asa Sandelius, Kaj Blennow, Henrik Zetterberg, Gassan Massarweh, Jean-Paul Soucy, A. Claudio Cuello, Serge Gauthier, Michael Waterston, Nathan Yoganathan, Etienne Lessard, Arsalan Haqqani, Kerry Rennie, Danica Stanimirovic, Balu Chakravarthy, Pedro Rosa-Neto
Summary: This study utilized in vivo longitudinal study design and a variety of biomarkers to evaluate the efficacy of a novel brain-penetrating anti-amyloid fusion protein treatment in a transgenic rat model of Alzheimer's disease. The treatment significantly reduced brain amyloid-beta levels and improved related biomarkers.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Wael Alata, Alvaro Yogi, Eric Brunette, Christie E. Delaney, Henk van Faassen, Greg Hussack, Umar Iqbal, Kristin Kemmerich, Arsalan S. Haqqani, Maria J. Moreno, Danica B. Stanimirovic
Summary: The study demonstrates the development of technologies targeting the blood-brain barrier to allow drugs to enter the brain. Through in vitro and in vivo experiments, the researchers showed the effectiveness of these technologies and their potential in pain treatment.
Article
Chemistry, Multidisciplinary
Etienne Lessard, Kerry Rennie, Arsalan Haqqani, Binbing Ling, James Whitfield, Andrea Paradis, Joseph Araujo, Nathan Yoganathan, John Gillard, Danica Stanimirovic, Balu Chakravarthy
Summary: This study demonstrates the translational attributes of the BBB-crossing A beta-targeting biotherapeutic KG207-H in eliciting a pharmacodynamic response, from rodents to larger animal species. The study compares the PK/PD of KG207-H in wild type rat and beagle dogs and shows similar serum pharmacokinetics and CNS exposure in both species.
PHARMACEUTICAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Jennifer J. Hill, Arsalan S. Haqqani, Danica B. Stanimirovic
Summary: Proteomic techniques have provided insights into the unique protein organization at the blood-brain barrier, particularly focusing on cellular components and transport mechanisms. In vivo proteomics approaches involve capturing luminal proteins for analysis using mass spectrometry-based methods, contributing to the development of novel delivery methods across the BBB.
Article
Clinical Neurology
AmanPreet Badhwar, Arsalan S. Haqqani
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
(2020)
Article
Neurosciences
Judie B. Alimonti, Maria Ribecco-Lutkiewicz, Caroline Sodja, Anna Jezierski, Danica B. Stanimirovic, Qing Liu, Arsalan S. Haqqani, Wayne Conlan, Mahmud Bani-Yaghoub
FLUIDS AND BARRIERS OF THE CNS
(2018)