Article
Oncology
Mario F. Munoz Pinto, Sandra J. Campbell, Christina Simoglou Karali, Vanessa A. Johanssen, Claire Bristow, Vinton W. T. Cheng, Niloufar Zarghami, James R. Larkin, Maria Pannell, Arron Hearn, Cherry Chui, Barbara Brinquis Nunez, Evert Bokma, Robert Holgate, Daniel C. Anthony, Nicola R. Sibson
Summary: The research team has developed a clinically translatable mutTNF that selectively opens the BBB at micrometastatic sites, providing a potential treatment window for brain metastasis that currently does not exist.
Article
Pharmacology & Pharmacy
Laura Rue, Tom Jaspers, Isabelle M. S. Degors, Sam Noppen, Dominique Schols, Bart De Strooper, Maarten Dewilde
Summary: The blood-brain barrier poses a challenge for the treatment of neurological diseases. Researchers have discovered two nanobodies that can bind to both human and cynomolgus transferrin receptors, potentially increasing the brain permeability of therapeutic drugs.
Article
Chemistry, Multidisciplinary
Sho Sato, Siyu Liu, Akihiko Goto, Tomoki Yoneyama, Koki Okita, Syunsuke Yamamoto, Hideki Hirabayashi, Shinji Iwasaki, Hiroyuki Kusuhara
Summary: Transferrin receptor (TfR)-mediated transcytosis is a promising drug delivery pathway for treating central nervous system diseases. However, the optimal drug profile for efficient delivery to the brain via TfR has not been fully understood, especially considering species-related differences. To address this, an advanced physiologically based pharmacokinetic (PBPK) model was developed to simulate the trans- and intracellular disposition of anti-TfR antibodies in the brain. The model was successfully calibrated using data from rats, monkeys, and human TfR knock-in (hTfR-KI) mice, and sensitivity analysis revealed important factors for optimal brain delivery.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Engineering, Biomedical
Marie Piantino, Fiona Louis, Yukari Shigemoto-Mogami, Kimiko Kitamura, Kaoru Sato, Tomoko Yamaguchi, Kenji Kawabata, Syunsuke Yamamoto, Shinji Iwasaki, Hideki Hirabayashi, Michiya Matsusaki
Summary: This study compared HBEC and hiPS-BMEC and found that hiPS-BMEC had higher expressions of transporters and tight junction proteins, resembling the BBB more accurately. Additionally, it confirmed the presence of transferrin receptor in hiPS-BMEC and its functionality in the RMT pathway.
MATERIALS TODAY BIO
(2022)
Review
Engineering, Biomedical
Xing Tian, Taojian Fan, Wentian Zhao, Ghulam Abbas, Bo Han, Ke Zhang, Nan Li, Ning Liu, Weiyuan Liang, Hao Huang, Wen Chen, Bing Wang, Zhongjian Xie
Summary: This review focuses on the potential applications of nanotechnology in stroke treatment. It discusses the main molecular pathological mechanisms of ischemic stroke, the role of the blood-brain barrier, and summarizes the challenges and future prospects of nanomedicine-based stroke treatments.
BIOACTIVE MATERIALS
(2021)
Article
Chemistry, Medicinal
William M. Pardridge, Tom Chou
Summary: This study examines the receptor-mediated transcytosis of monoclonal antibodies targeting transferrin receptor or insulin receptor at the blood-brain barrier, using mathematical models to analyze and predict the transport process. The optimal rates of receptor association with the targeted antibodies are highlighted as crucial factors determining the efficiency of transcytosis.
Article
Medicine, Research & Experimental
Alex Petrovic, Nicole G. Metzendorf, Fadi Rofo, Canan U. Yilmaz, Sofia Stenler, Hanna Laudon, Jamie I. Morrison, Greta Hultqvist
Summary: This study developed an in vitro BBB model based on murine cells to evaluate the BBB-penetrating capabilities of transferrin-receptor-targeting antibodies. The results showed that the conjugated antibodies were more effectively transported in the model compared to unconjugated antibodies. The model can be used as a preclinical screening platform for therapeutic neurological pathologies.
MOLECULAR PHARMACEUTICS
(2023)
Article
Multidisciplinary Sciences
Danny D. Sahtoe, Adrian Coscia, Nur Mustafaoglu, Lauren M. Miller, Daniel Olal, Ivan Vulovic, Ta-Yi Yu, Inna Goreshnik, Yu-Ru Lin, Lars Clark, Florian Busch, Lance Stewart, Vicki H. Wysocki, Donald E. Ingber, Jonathan Abraham, David Baker
Summary: The challenge of designing polar protein-protein interactions is addressed by a computational approach utilizing complementary geometrically matched beta strands. Specifically designed proteins successfully bind to the human transferrin receptor, enabling drug delivery across the blood-brain barrier. This design strategy offers a general approach for creating binders to protein targets with exposed surface beta edge strands.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Rikke B. Hansen, Cathrine C. H. Laursen, Niala Nawaz, Jonna S. Madsen, Helle H. Nielsen, Christina Kruuse, Arne Moller, Matilda Degn, Kate L. Lambertsen
Summary: Plasma levels of TNFR1 and TNFR2 are significantly elevated in patients with ischemic stroke, but show no correlation with patient outcome measurements. After ischemic stroke, patients had decreased populations of non-classical monocytes and neutrophils expressing TNFR1, increased neutrophils expressing TNFR2, and decreased non-classical populations co-expressing both TNFR1 and TNFR2.
Article
Immunology
Eldar Hochman, Michal Taler, Reut Flug, Shay Gur, Shira Dar, Gil Bormant, Dori Blattberg, Uri Nitzan, Amir Krivoy, Abraham Weizman
Summary: Accumulating evidence suggests that inflammation and NVU dysfunction disrupt BBB integrity and contribute to depression. The endothelial protein Claudin-5, which is involved in BBB integrity, has been implicated in psychiatric disorders including MDD and schizophrenia. In an animal model, the pro-inflammatory cytokine TNF-alpha was found to affect BBB permeability and claudin-5 expression. This study is the first to assess the relationship between serum levels of claudin-5 and TNF-alpha during MDEs. The results showed significantly higher levels of claudin-5 and TNF-alpha in MDE patients compared to healthy controls, suggesting a possible specific interaction between claudin-5 and TNF-alpha in depression pathogenesis.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Article
Chemistry, Medicinal
William M. Pardridge
Summary: Biologic drugs are large molecule pharmaceuticals that cannot cross the blood-brain barrier. They can be re-engineered for BBB transport as IgG fusion proteins. The kinetics of BBB transport can be quantified with mathematical models.
Article
Cell Biology
Stephanie L. Baringer, Kondaiah Palsa, Vladimir S. Spiegelman, Ian A. Simpson, James R. Connor
Summary: Using cell culture techniques, this study investigates the mechanism by which apo- and holo-Tf influence iron release from endothelial cells. It is found that holo-Tf induces ferroportin internalization, while apo-Tf directly interacts with hephaestin. Only pathophysiological levels of hepcidin disrupt the interaction between holo-Tf and ferroportin. These findings provide a molecular mechanism for the regulation of iron release.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Barrett D. Allen, Charles L. Limoli
Summary: Exposure to radiation during the treatment of CNS tumors leads to detrimental damage of the blood brain barrier (BBB) in normal tissue, while the irregular vasculature of the blood tumor barrier (BTB) causes tumor tissue to become resistant to radiation.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Hui-min Gao, Hao Chen, Gui-Yun Cui, Jin-Xia Hu
Summary: This article briefly describes the role and mechanism of action of the blood-brain barrier (BBB), as well as the functional proteins involved. Additionally, it discusses the mechanisms of BBB damage following an ischemic stroke and presents several therapeutic strategies addressing these impairments. The article aims to provide innovative ideas for drug delivery research via the BBB.
CELL AND BIOSCIENCE
(2023)
Article
Acoustics
Marieke Olsman, Viktoria Sereti, Melina Muhlenpfordt, Kasper Bendix Johnsen, Thomas Lars Andresen, Andrew James Urquhart, Catharina De Lange Davies
Summary: Research shows that combining FUS and microbubbles with BBB-targeting liposomes can enhance drug delivery to the brain. Transferrin receptor-targeting liposomes exhibited increased accumulation in the FUS-treated hemisphere, while isotype immunoglobulin G liposomes did not show significant increase.
ULTRASOUND IN MEDICINE AND BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Hungyen Lee, Dahai Jiang, William M. Pardridge
MOLECULAR PHARMACEUTICS
(2020)
Review
Physiology
William M. Pardridge
FRONTIERS IN PHYSIOLOGY
(2020)
Article
Medicine, Research & Experimental
Joshua Yang, Jiahong Sun, Demi M. Castellanos, William M. Pardridge, Rachita K. Sumbria
MOLECULAR PHARMACEUTICS
(2020)
Article
Multidisciplinary Sciences
Dahai Jiang, Hungyen Lee, William M. Pardridge
SCIENTIFIC REPORTS
(2020)
Article
Pharmacology & Pharmacy
Demi M. Castellanos, Jiahong Sun, Joshua Yang, Weijun Ou, Alexander C. Zambon, William M. Pardridge, Rachita K. Sumbria
Review
Chemistry, Medicinal
William M. Pardridge
Article
Chemistry, Medicinal
William M. Pardridge, Tom Chou
Summary: This study examines the receptor-mediated transcytosis of monoclonal antibodies targeting transferrin receptor or insulin receptor at the blood-brain barrier, using mathematical models to analyze and predict the transport process. The optimal rates of receptor association with the targeted antibodies are highlighted as crucial factors determining the efficiency of transcytosis.
Article
Chemistry, Medicinal
William M. Pardridge
Summary: Biologic drugs are large molecule pharmaceuticals that cannot cross the blood-brain barrier. They can be re-engineered for BBB transport as IgG fusion proteins. The kinetics of BBB transport can be quantified with mathematical models.
Review
Pharmacology & Pharmacy
William M. Pardridge
Summary: The majority of lysosomal storage diseases affect the brain. The current intravenous enzyme replacement therapy is not effective because the recombinant lysosomal enzymes cannot cross the blood-brain barrier (BBB). However, by re-engineering biologic drugs into IgG-enzyme fusion proteins, it is possible to deliver the lysosomal enzymes to the brain through the BBB. This approach utilizes the IgG domain of the fusion protein, which acts as a molecular Trojan horse to transport the lysosomal enzymes across the BBB.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Review
Pharmacology & Pharmacy
William M. Pardridge
Summary: This article reviews the history of brain drug delivery and discusses different technologies and methods. Due to the restricted transport across the blood-brain barrier, FDA-approved drugs for the central nervous system are generally limited to lipid-soluble small molecules.
Editorial Material
Pharmacology & Pharmacy
William M. Pardridge
Article
Genetics & Heredity
Andreas Hahn, Yuji Sato, Toshiaki Ikeda, Hiroyuki Sonoda, Mathias Schmidt, Charlotte Pfrimmer, Ruben J. Boado, William M. Pardridge
Summary: This study reports the case of a boy with CLN1 disease who showed improvement in life quality and seizure control after treatment with an intravenous BBB penetrating enzyme replacement therapy.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2022)
Article
Chemistry, Multidisciplinary
William M. M. Pardridge
Summary: A physiologically based pharmacokinetic (PBPK) model was developed to study drug association and dissociation with plasma proteins and brain tissue proteins, as well as drug permeability at the blood-brain barrier. The model evaluated the impact of plasma protein-mediated uptake on the concentration of free drug in the brain and studied the effect of drug binding to brain tissue proteins on free drug concentration in the brain.
PHARMACEUTICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
William M. Pardridge
Summary: The COVID-19 mRNA vaccine uses scalable manufacturing of lipid nanoparticles (LNPs) to encapsulate mRNA. This large nucleic acid delivery technology has potential applications in gene therapy, including delivering plasmid DNA. To enable gene therapy for the brain, LNPs could be reformulated for brain delivery by attaching receptor-specific monoclonal antibodies (MAbs) to the LNP surface. The MAbs act as molecular Trojan horses, facilitating the transport of LNPs across the blood-brain barrier (BBB) and localization to the nucleus for therapeutic gene transcription.
TRENDS IN MOLECULAR MEDICINE
(2023)
Review
Engineering, Biomedical
William M. Pardridge
FRONTIERS IN MEDICAL TECHNOLOGY
(2020)
Article
Neurosciences
Xiaomei Lin, Tianyuyi Feng, Erheng Cui, Yunfei Li, Zhang Qin, Xiaohu Zhao
Summary: This study successfully established a rat model based on the genetic-environmental interaction, which exhibited phenotype characteristics similar to human AD in terms of cognitive function, brain microstructure, and immunohistochemistry. The genetic factor (APP mutation) and the environmental factor (acrolein exposure) accounted for 39.74% and 33.3% of the AD-like phenotypes in the model, respectively.
Article
Neurosciences
Gustavo Guimara Guerrero, Giovanna Bignoto Minhoto, Camilla dos Santos Tiburcio-Machado, Itza Amarisis Ribeiro Pinto, Claudio Antonio Federico, Marcia Carneiro Valera
Summary: The present study evaluated the influence of head and neck radiotherapy on the behavior and body weight gain in Wistar rats. The results demonstrated that different doses of radiation induced depressive behavior in the animals, and that the weight gain tended to be lower in the irradiated groups.
Article
Neurosciences
Ziwei Gao, Chao Lu, Yaping Zhu, Yuxin Liu, Yuesong Lin, Wenming Gao, Liyuan Tian, Lei Wu
Summary: This study reveals the underlying mechanisms of the rapid antidepressant effects of merazin hydrate (MH), which activates CaMKII to promote neuronal activities and proliferation in the hippocampus.
Article
Neurosciences
Kathleen E. Murray, Whitney A. Ratliff, Vedad Delic, Bruce A. Citron
Summary: Gulf War Illness (GWI) is a chronic disorder that affects approximately 30% of Veterans deployed to the Persian Gulf. This study found that exposure to toxicants during the Gulf War resulted in long-term changes in the morphology of dentate granule cells and that treatment with Nrf2 activator could improve neuronal health in the hippocampus.
Article
Neurosciences
Jing Li, Yan Zou, Xiangchuang Kong, Yangming Leng, Fan Yang, Guofeng Zhou, Bo Liu, Wenliang Fan
Summary: This study examines the functional connectivity changes in individuals with sudden sensorineural hearing loss (SSNHL) at the integrity, network, and edge levels. The findings reveal reduced intranetwork connectivity strength and increased internetwork connectivity in SSNHL patients. These alterations are associated with the duration of SSNHL and Tinnitus Handicap Inventory scores. The study provides crucial insights into the neural mechanisms of SSNHL and the brain's network-level responses to sensory loss.
Review
Neurosciences
Didier Majou, Anne-Lise Dermenghem
Summary: In the early stages of SAD, memory impairment is strongly correlated with cortical levels of soluble amyloid-beta peptide oligomers. A beta disrupts glutamatergic synaptic function and leads to cognitive deficits. This article describes the pathogenic mechanisms underlying cerebral amyloidosis, involving amyloid precursor protein synthesis, A beta residue clearance processes, and the role of specific molecules.
Article
Neurosciences
Jing Li, Yi Shan, Xiaojing Zhao, Guixiang Shan, Peng-Hu Wei, Lin Liu, Changming Wang, Hang Wu, Weiqun Song, Yi Tang, Guo-Guang Zhao, Jie Lu
Summary: This study investigates changes in brain anatomical structures and functional network connectivity after chronic complete thoracic spinal cord injury (cctSCI) and their impact on clinical outcomes. The findings reveal alterations in gray matter volume and functional connectivity in specific brain regions, indicating potential therapeutic targets and methods for tracking treatment outcomes.
Article
Neurosciences
Anllely Fernandez, Katherine Corvalan, Octavia Santis, Maxs Mendez-Ruette, Ariel Caviedes, Matias Pizarro, Maria -Teresa Gomez, Luis Federico Batiz, Peter Landgraf, Thilo Kahne, Alejandro Rojas-Fernandez, Ursula Wyneken
Summary: This study reveals the importance of SUMOylation in modulating the protein cargo of astrocyte-derived small extracellular vesicles (sEVs) and its potential impact on neurons.
Article
Neurosciences
Anika Luettig, Stefanie Perl, Maria Zetsche, Franziska Richter, Denise Franz, Marco Heerdegen, Ruediger Koehling, Angelika Richter
Summary: This study found that changes in c-Fos activity during short-term stimulation of the entopeduncular nucleus (EPN) are associated with improvement in dystonia, and also discovered that the cerebellum may be involved in the antidystonic effects.
Article
Neurosciences
Yanlin Tao, Wei Shen, Houyuan Zhou, Zikang Li, Ting Pi, Hui Wu, Hailian Shi, Fei Huang, Xiaojun Wu
Summary: Depression has a higher incidence in women compared to men, and this study investigated the impact of sex on depressive behaviors and underlying mechanisms using a corticosterone-induced depression model in mice. The results showed sex-specific anxiety and depression behaviors in the model group, as well as differences in protein expression and neurotransmitter levels between male and female mice. These findings enhance our understanding of sex-specific differences in depression and support tailored interventions.
Review
Neurosciences
Dnyandev G. Gadhave, Vrashabh V. Sugandhi, Chandrakant R. Kokare
Summary: This article discusses the characteristics and importance of the tight junctions of endothelial cells in the CNS, which act as a biological barrier known as the blood-brain barrier (BBB). It focuses on overcoming the challenges of delivering therapeutic agents to the brain in neurodegenerative disorders, particularly multiple sclerosis, through the use of biomaterials. The article also highlights the current limitations of animal models for studying multiple sclerosis and suggests a potential future research direction.
Article
Neurosciences
Li-Min Mao, Khyathi Thallapureddy, John Q. Wang
Summary: Propofol can enhance synapsin phosphorylation and modulate synaptic transmission in the mouse brain. The study reveals the potential role of synapsin as a substrate of propofol and its effects on neurotransmitter release machinery.
Article
Neurosciences
Syed Maaz Ahmed Rizvi, Abdul Baseer Buriro, Irfan Ahmed, Abdul Aziz Memon
Summary: This study explores the effects of prolonged mask usage on the human brain by analyzing EEG and physiological parameters. The results show that the mean EEG spectral power in alpha, beta, and gamma sub-bands of individuals wearing masks is smaller than those without masks. The performances on cognitive tasks and oxygen saturation level differ between the two groups, while blood pressure, body temperature, and heart rate are similar. The analysis also reveals that the occipital and frontal lobes exhibit the greatest variability in channel measurements.
Article
Neurosciences
Rui-Fang Ma, Lu-Lu Xue, Jin-Xiang Liu, Li Chen, Liu-Lin Xiong, Ting-Hua Wang, Fei Liu
Summary: This study observed changes in brain infarction and blood vessels in rats during neonatal hypoxic ischemic encephalopathy (NHIE) modeling using Transcranial Doppler Ultrasonography (TCD). Longer duration of hypoxia was associated with more severe nerve damage. TCD can dynamically monitor cerebral infarction after NHIE modeling, which may serve as a useful auxiliary method for evaluating animal experimental models.
Article
Neurosciences
Yuxiang Dai, Chen Yu, Lu Zhou, Longyang Cheng, Hongbin Ni, Weibang Liang
Summary: Overexpression of CXCR4 in glioma is correlated with patient survival, and its inhibition can reduce invasion and migration of glioma cells. Inhibiting Nur77 also decreases cancer progression associated with CXCR4.
