Article
Environmental Sciences
Cyril Willson
Summary: Testosterone is the main androgen in men and plays important physiological roles. It is used for testosterone replacement therapy (TRT) but also abused for cosmetic and performance-enhancing purposes. There have been speculations that testosterone may cause neurological damage. However, the available in vitro and observational data are limited and provide weak evidence to support the claim that testosterone use or abuse has neurotoxic potential in humans. More research is needed to gain a better understanding.
Article
Neurosciences
Yuying Cen, Yuheng Shan, Jiahua Zhao, Xiaojiao Xu, Zhiyong Nie, Jiatang Zhang
Summary: This study aimed to investigate the impact of major transporters at the blood-brain barrier and blood-cerebrospinal fluid barrier on the pharmacokinetics of levofloxacin in rats. The results showed that the efflux of levofloxacin from the central nervous system involves multi-drug resistance-associated proteins, breast cancer resistance protein, and organic anion transporters. The concentrations of levofloxacin in cerebrospinal fluid can be used as a surrogate to predict the concentrations inside the brain parenchyma.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Aaro J. Jalkanen, Jouni Ihalainen, Marko Lehtonen, Markus M. Forsberg, Jarkko Rautio, Kristiina M. Huttunen, Mikko Gynther
Summary: The study found significant species differences in the intra-brain distribution of compounds utilizing L-type amino acid transporter 1 between mice and rats, with more pronounced effects in rats. These results underscore the importance of cross-species characterization of prodrug pharmacokinetics and pharmacodynamics in preclinical studies.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Mohammed A. A. Saleh, Elizabeth C. M. de Lange
Summary: This study investigated the impact of altered cerebral blood flow, tight junction paracellular pore radius, brain extracellular fluid volume, and pH values on drug transport and concentrations in the central nervous system. The results showed drug-dependent effects of pathophysiological changes on blood-brain barrier transport and drug concentrations within the brain extracellular and intracellular fluid. Changes in pore radius, pH values, and blood flow affected the rate and extent of drug transport, highlighting the importance of considering these factors in drug delivery to the brain.
Review
Pharmacology & Pharmacy
Samuel A. Sprowls, Pushkar Saralkar, Tasneem Arsiwala, Christopher E. Adkins, Kathryn E. Blethen, Vincenzo J. Pizzuti, Neal Shah, Ross Fladeland, Paul R. Lockman
Summary: The article discusses the role of blood-brain barrier (BBB) and the determination of K-in values, highlighting their application in various pathological conditions. Furthermore, it compares experimental results with human parallels to validate the data.
Article
Physiology
Caitlin Brown, Sarah Pemberton, Alice Babin, Noor Abdulhameed, Cassidy Noonan, Mary Beth Brown, William A. Banks, Elizabeth M. Rhea
Summary: Exercise enhances insulin blood-brain barrier transport, improving cognition independent of changes in serum factors.
JOURNAL OF APPLIED PHYSIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Yong Zhang, Sejal Sharma, Shirisha Jonnalagadda, Shikha Kumari, Aarfa Queen, Shiva Hadi Esfahani, Sabrina Rahman Archie, Saeideh Nozohouri, Dhavalkumar Patel, Paul C. Trippier, Vardan T. Karamyan, Thomas J. Abbruscato
Summary: This study provides essential details about the pharmacokinetic properties of a new generation of potent non-peptidomimetic Nln activators with high BBB permeability, which warrants their future development as potential neuroprotective pharmaceutics for stroke treatment.
PHARMACEUTICAL RESEARCH
(2023)
Article
Oncology
Victor Moreno, Juan Manuel Sepulveda, David A. Reardon, Angel Perez-Nunez, Pedro Gonzalez Leon, Bishoy Hanna, Ellen Filvaroff, Ida Aronchik, Henry Chang, Barbara Amoroso, Marlene Zuraek, Tania Sanchez-Perez, Cristina Mendez, Daniel Stephens, Zariana Nikolova, Michael A. Vogelbaum
Summary: This study investigates the pharmacokinetics, pharmacodynamics, and CNS penetration of the BET inhibitor trotabresib in patients with recurrent high-grade gliomas. The results show that trotabresib penetrates the blood-brain-tumor barrier and demonstrates target engagement in resected tumor tissue. The pharmacokinetics, pharmacodynamics, and safety of trotabresib in these patients are comparable to previous results in patients with advanced solid tumors.
Review
Pharmacology & Pharmacy
Md Masud Parvez, Armin Sadighi, Yeseul Ahn, Steve F. Keller, Julius O. Enoru
Summary: Uptake drug transporters in the brain play a significant role in drug metabolism, and understanding their contribution to drug entry into the central nervous system is crucial for clinical translation and drug development. However, species differences may affect the translation between humans and animals.
Article
Pharmacology & Pharmacy
Saurabh Shah, Paras Famta, Deepkumar Bagasariya, Kondasingh Charankumar, Etikala Amulya, Dharmendra Kumar Khatri, Rajeev Singh Raghuvanshi, Shashi Bala Singh, Saurabh Srivastava
Summary: The era of nanomedicine has made significant breakthroughs in the treatment of disorders. Tuning nanoparticle shape and geometry is crucial for overcoming challenges in therapeutics and biomedical fields.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Immunology
Swati Shah, Mitchell L. Turner, Xueyi Chen, Beau M. Ances, Dima A. Hammoud, Elizabeth W. Tucker
Summary: Diagnosis, monitoring, and assessing response to therapy of CNS infections is challenging. Molecular imaging techniques can complement anatomic imaging for studying the development and treatment response of CNS infections. Pathogen-specific radiotracers can accurately diagnose CNS infections and have the potential to cross the blood-brain barrier.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Pharmacology & Pharmacy
Arthur J. J. van de Vyver, Antje-Christine Walz, Mariette S. S. Heins, Afsaneh Abdolzade-Bavil, Thomas E. E. Kraft, Inja Waldhauer, Michael B. B. Otteneder
Summary: Monoclonal antibodies play a vital role in the treatment of diseases, but their development for neurological disorders in the brain is challenging. This study investigated the pharmacokinetics of a bispecific monoclonal antibody in the brain of rats using different administration routes. The researchers developed a model to quantify the drug uptake and found that the blood-cerebrospinal fluid barrier impedes antibody transfer. The study suggests that intravenous administration may achieve higher local drug exposure compared to intracerebroventricular administration.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Nikolas Bergum, Casey-Tyler Berezin, Gregory Dooley, Jozsef Vigh
Summary: This study measured the levels of morphine in the retina of mice after systemic exposure and found that morphine accumulates in the retina for a longer time and at higher concentrations than in the brain. These findings suggest that chronic use of opioid drugs can lead to morphine accumulation in the retina, which may have detrimental effects on visual functions.
Review
Clinical Neurology
Roland Nau, Fritz Sorgel, Helmut Eiffert
Summary: Antimicrobial resistance poses a growing threat to patients, including those with nosocomial central nervous system infections. Optimizing intravenous treatment to achieve sufficient concentrations of antibiotics in different CNS compartments is crucial when causative pathogens have reduced sensitivity to antibiotics or the blood-brain barrier is mildly impaired. Adjusting antibiotic doses and exploring new combinations have shown promise in addressing antimicrobial resistance in CNS infections.
CURRENT OPINION IN NEUROLOGY
(2021)
Article
Pharmacology & Pharmacy
Qun Wang, Rui Ma, Piaoxue Liu, Guowang Cheng, Qi Yang, Xiaojia Chen, Zhenfeng Wu, Dongsheng Yuan, Tongkai Chen
Summary: This study developed biodegradable nanoparticles to deliver Ginkgolide B as a treatment for Parkinson's disease. The nanoparticles showed sustained drug release and protected against neuronal cytotoxicity. Pharmacokinetic studies demonstrated higher accumulation of the nanoparticles in plasma and brain. Animal models also showed positive outcomes with this nanoparticle treatment.
Review
Medicine, Research & Experimental
Aric F. Logsdon, Elizabeth M. Rhea, May Reed, William A. Banks, Michelle A. Erickson
Summary: The endothelial glycocalyx layer (EGL) is a crucial component of the blood-brain barrier (BBB), consisting of proteoglycans and glycosaminoglycans. It serves as the first line of defense in preventing substances from entering the brain.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2021)
Review
Endocrinology & Metabolism
Elizabeth M. Rhea, William A. Banks
Summary: Since the discovery of insulin in 1921, research has extensively investigated its role in the brain, particularly its ability to regulate peripheral glucose levels and transport across the blood-brain barrier. Advancements in technology have allowed for quantitative measurement of insulin transport rate at the blood-brain barrier, as well as exploration of the specific role of the insulin receptor through genetic mouse models and high-specificity antagonists.
JOURNAL OF NEUROENDOCRINOLOGY
(2021)
Article
Neurosciences
Elizabeth M. Rhea, Aric F. Logsdon, Kim M. Hansen, Lindsey M. Williams, May J. Reed, Kristen K. Baumann, Sarah J. Holden, Jacob Raber, William A. Banks, Michelle A. Erickson
Summary: The study demonstrates that the SARS-CoV-2 spike 1 protein can cross the mouse blood-brain barrier and be taken up by both the brain and peripheral tissues. Intravenous injection results in higher levels of protein uptake in the brain compared to intranasal administration. Genetic factors and sex have varying effects on the uptake of the spike protein in different tissues.
NATURE NEUROSCIENCE
(2021)
Article
Clinical Neurology
Aric F. Logsdon, Kendra L. Francis, Nicole E. Richardson, Shannon J. Hu, Chelsea L. Faber, Bao Anh Phan, Vy Nguyen, Naly Setthavongsack, William A. Banks, Randy L. Woltjer, C. Dirk Keene, Caitlin S. Latimer, Michael W. Schwartz, Jarrad M. Scarlett, Kimberly M. Alonge
Summary: The study found that patients with AD-related dementia experience a re-coding of their PNN-associated CS-GAGs, correlating with the progression of pathology, accumulation of p-tau, and cognitive impairment. These sulfation changes can be detected prior to classical AD pathology, potentially playing a crucial role in the development of the disease.
ALZHEIMERS & DEMENTIA
(2022)
Review
Biochemistry & Molecular Biology
Melvin R. Hayden, William A. Banks
Summary: Obesity, metabolic syndrome, type 2 diabetes, and aging are global societal problems with potential complications, causing economic burdens to individuals and families. This review focuses on the role of leptin hormone from white adipose tissue in brain remodeling in female mice with hyperphagia, obesity, or hyperglycemia, examining structural changes in various brain components.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Chemistry, Multidisciplinary
Elizabeth M. Rhea, William A. Banks
Summary: The interactions between lipids, lipoproteins, and apolipoproteins with the blood-brain barrier (BBB) are diverse and important for both health and disease.
PHARMACEUTICAL RESEARCH
(2021)
Review
Chemistry, Multidisciplinary
Jia Li, Meng Zheng, Olga Shimoni, William A. Banks, Ashley I. Bush, Jennifer R. Gamble, Bingyang Shi
Summary: The blood-brain barrier is a crucial neurovascular unit that prevents harmful substances from entering the brain and maintains normal neuronal function. Disruption of BBB in diseases can contribute to disease progression, while restoration of BBB integrity is a biomarker for better clinical outcomes. The BBB also plays a role in facilitating communication between neuronal and circulatory systems, showing promising results for brain-targeted drug delivery.
Editorial Material
Biotechnology & Applied Microbiology
Jia Li, Meng Zheng, Yan Zou, Pu Chun Ke, Miqin Zhang, William A. Banks, Bingyang Shi
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Takashi Fujimoto, Yoichi Morofuji, Andrej Kovac, Michelle A. Erickson, Maria A. Deli, Masami Niwa, William A. Banks
Summary: Statins have neuroprotective effects on neurological diseases, possibly through regulating blood-brain barrier function. Pitavastatin (PTV) can ameliorate lipopolysaccharide-induced blood-brain barrier dysfunction by inhibiting cytokine production. These findings highlight the pharmacological significance of statins in the treatment of central nervous system diseases.
Article
Multidisciplinary Sciences
Elizabeth M. Rhea, Kim Hansen, Sarah Pemberton, Eileen Ruth S. Torres, Sarah Holden, Jacob Raber, William A. Banks
Summary: Independent risk factors such as age, apoE isoform, sex, and diet can impact the development of Alzheimer's disease. Synergies between some of these risk factors have been observed, but the relationship between the latter three has not been studied. Analysis of the insulin blood-brain barrier pharmacokinetics in aged male and female mice with different apoE isoforms and diets showed potential differences in insulin interactions, which may contribute to cognitive changes related to altered CNS insulin signaling.
SCIENTIFIC REPORTS
(2021)
Review
Medicine, Research & Experimental
Michelle A. Erickson, William A. Banks
Summary: Disruption of the blood-brain barrier (BBB) can occur through different mechanisms and pathways, resulting in different neurological insults. The importance of transcellular pathways in BBB disruption has been highlighted. Transcytotic mechanisms are less clearly linked to permeability compared to membrane spanning canaliculi and fenestrations. Cellular components involved in transcellular mechanisms of BBB disruption are being discovered and measured, adding to our classic knowledge based on ultrastructural studies.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2022)
Article
Pharmacology & Pharmacy
William A. Banks, Pericles Calias, Kim M. Hansen, Kristin M. Bullock, Kory Engelke
Summary: This study evaluated the uptake and distribution of kleptose in the brain and spinal cord after intranasal and intrathecal delivery. The results showed that intrathecal delivery resulted in higher distribution in the brain compared to intranasal delivery.
JOURNAL OF PHARMACY AND PHARMACOLOGY
(2022)
Review
Medicine, Research & Experimental
Rachel C. Knopp, Michelle A. Erickson, Elizabeth M. Rhea, May J. Reed, William A. Banks
Summary: The blood-brain barrier (BBB) is an important interface that regulates communication between the brain and blood. It is comprised of brain endothelial cells and is surrounded by supportive brain cell types. Recent studies have shown that the BBB undergoes dysfunction during aging and in diseases, and cellular senescence, one of the hallmarks of aging, is believed to play a role in these changes. This review summarizes the known age-related changes at the BBB, evaluates the impact of cellular senescence in neurodegenerative diseases, discusses insights from in vitro and in vivo studies, and explores mechanisms by which cellular senescence affects BBB function.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2023)
Article
Geriatrics & Gerontology
Subhashis Banerjee, Sarbani Ghoshal, Clemence Girardet, Kelly M. DeMars, Changjun Yang, Michael L. Niehoff, Andrew D. Nguyen, Prerana Jayanth, Brittany A. Hoelscher, Fenglian Xu, William A. Banks, Kim M. Hansen, Jinsong Zhang, Eduardo Candelario-Jalil, Susan A. Farr, Andrew A. Butler
Summary: Studies have shown that adropin is highly expressed in the human brain and plays a crucial role in neural network development and function. In elderly individuals, adropin is positively correlated with genes related to mitochondrial function, morphogenesis, and inflammation, while cognitive decline can be reversed by increasing adropin expression.
NPJ AGING AND MECHANISMS OF DISEASE
(2021)
Review
Cell Biology
William A. Banks, May J. Reed, Aric F. Logsdon, Elizabeth M. Rhea, Michelle A. Erickson
Summary: The blood-brain barrier undergoes changes in morphology and function during healthy aging, affecting communication and homeostatic regulation between the brain and peripheral tissues, and potentially predisposing to age-related diseases.