Article
Clinical Neurology
Bruna Bellaver, Albert Puig-Pijoan, Joao Pedro Ferrari-Souza, Douglas T. Leffa, Firoza Z. Lussier, Pamela C. L. Ferreira, Cecile Tissot, Guilherme Povala, Joseph Therriault, Andrea L. Benedet, Nicholas J. Ashton, Stijn Servaes, Mira Chamoun, Jenna Stevenson, Nesrine Rahmouni, Marie Vermeiren, Arthur C. Macedo, Aida Fernandez-Lebrero, Greta Garcia-Escobar, Irene Navalpotro-Gomez, Oscar Lopez, Dana L. Tudorascu, Ann Cohen, Victor L. Villemagne, William E. Klunk, Serge Gauthier, Eduardo R. Zimmer, Thomas K. Karikari, Kaj Blennow, Henrik Zetterberg, Marc Suarez-Calvet, Pedro Rosa-Neto, Tharick A. Pascoal
Summary: The permeability of the blood-brain barrier (BBB) may affect the levels of brain-derived proteins in the blood, which in turn can impact the relationship between brain and blood biomarkers. The study found that BBB permeability influenced the relationship between plasma A beta(42/40) and CSF A beta(42/40) as well as A beta-PET positivity, but did not significantly impact the relationship between brain and plasma p-tau levels.
ALZHEIMERS & DEMENTIA
(2023)
Article
Cell Biology
Tong Wu, Lizhi Chen, Lingqi Zhou, Jie Xu, Kaihua Guo
Summary: Platelets may play an important role in the pathogenesis of Alzheimer's disease, as their Aβ content increases with age and aged platelets can accelerate Aβ deposition in the brain, leading to learning and memory deficits in recipient mice. Administering aspirin as a platelet activation inhibitor effectively alleviated these toxic processes. In vitro blood-brain barrier models were used to explore the possible cytotoxicity of these platelets.
Article
Biochemistry & Molecular Biology
Romain Versele, Emmanuel Sevin, Fabien Gosselet, Laurence Fenart, Pietra Candela
Summary: The blood-brain barrier is a crucial barrier for maintaining brain homeostasis, and cytokine-induced neuroinflammation may play a role in BBB dysfunction and contribute to the progression of Alzheimer's disease. Cytokines like TNF-alpha and IL-1 beta can modulate BBB permeability, leading to amyloid-beta peptide accumulation and potentially influencing the progression of AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Andrew L. Zhou, Nidhi Sharda, Vidur V. Sarma, Kristen M. Ahlschwede, Geoffry L. Curran, Xiaojia Tang, Joseph F. Poduslo, Krishna R. Kalari, Val J. Lowe, Karunya K. Kandimalla
Summary: Age-related changes in the plasma pharmacokinetics and brain influx of A beta isoforms and insulin may potentially increase the risk of Alzheimer's disease.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Alryel Yang, Amjad Z. Alrosan, Laura J. Sharpe, Andrew J. Brown, Richard Callaghan, Ingrid C. Gelissen
Summary: This study investigated the regulation of ABCG4 by oxysterols, cholesterol-synthesis intermediates and cholesterol itself, revealing that a synthetic LXR ligand induced ABCG4 expression in astrocytes, while cholesterol and cholesterol-synthesis intermediates stabilized ABCG4 protein. These findings provide new insights into the post-translational control of ABCG4 and its role in maintaining sterol homeostasis in the brain.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Pharmacology & Pharmacy
Stephanie Andrade, Maria J. Ramalho, Joana A. Loureiro, Maria C. Pereira
Summary: This study developed a VB12-loaded liposome nanosystem capable of dual-targeting VB12 to the blood-brain barrier (BBB) and neuronal cells, delaying the formation of Aβ fibrils and disrupting mature fibrils. This research has significant potential for the prevention and treatment of AD.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
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.
Article
Cell Biology
Peng Zhao, Yuanzhong Xu, Lulin Jiang, Xuejun Fan, Leike Li, Xin Li, Hisashi Arase, Yingjun Zhao, Wei Cao, Hui Zheng, Huaxi Xu, Qingchun Tong, Ningyan Zhang, Zhiqiang An
Summary: This study demonstrated the feasibility of engineering multivalent TREM2 agonistic antibody coupled with TfR-mediated brain delivery to enhance microglia functions and reduce amyloid pathology in vitro and in vivo.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Neurosciences
Kassandra Kisler, Abhay P. Sagare, Divna Lazic, Sam Bazzi, Erica Lawson, Ching-Ju Hsu, Yaoming Wang, Anita Ramanathan, Amy R. Nelson, Zhen Zhao, Berislav V. Zlokovic
Summary: PICALM is a significant susceptibility factor for Alzheimer's disease and plays a role in Aβ clearance at the blood-brain barrier. The anti-malaria drug artesunate can increase PICALM levels, reduce Aβ deposition, and improve cerebral blood flow and behavior in mice. This research is important for the treatment of Alzheimer's disease.
MOLECULAR NEURODEGENERATION
(2023)
Article
Pharmacology & Pharmacy
Yu-Chen Lo, Wen-Jen Lin
Summary: The study utilized a peptide-conjugated nano-delivery system to enhance penetration into tumor cells by overcoming the blood brain barrier. NPs conjugated with T7 peptide showed higher accumulation in the brain and lower biodistribution in nontarget tissues. The benefit of T7 peptide as a targeting ligand for NPs across the BBB was elucidated in this study.
Article
Neurosciences
Shingo Ito, Ryotaro Yagi, Seiryo Ogata, Takeshi Masuda, Takashi Saito, Takaomi Saido, Sumio Ohtsuki
Summary: This study investigates the relationship between blood-brain barrier (BBB) alterations and the progression of Alzheimer's disease (AD), focusing on the accumulation of amyloid-beta peptide (Aβ) in the brains of humanized amyloid precursor protein knock-in (APP-KI) mice. The study finds that BBB dysfunction occurs early in AD development, and changes in the BBB occur after advanced Aβ accumulation in the brain. These findings provide insights into the role of BBB alterations in AD progression.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Article
Biology
Jie Wang, Amir Rattner, Jeremy Nathans
Summary: Bacterial meningitis, particularly in infants and the elderly, can lead to serious illness and death. This study investigates the response of different types of meningeal cells to early postnatal E. coli infection in mice. The findings show that the transcriptomes of major meningeal cell types, including endothelial cells, macrophages, and fibroblasts, undergo distinct changes upon infection. Additionally, the study reveals alterations in the distribution of certain proteins and reduced blood-brain barrier integrity in leptomeningeal capillaries. The response to infection is largely driven by TLR4 signaling, and the EC response to E. coli infection is independent of the interaction between macrophages and ECs.
Article
Multidisciplinary Sciences
Qianqian Huang, Chaoqing Jiang, Xue Xia, Yufan Wang, Chenxing Yan, Xiaorong Wang, Ting Lei, Xiaotong Yang, Wenqin Yang, Guo Cheng, Huile Gao
Summary: Constructed multifunctional melanin-like metal ion chelators and neuroinflammation regulators (PDA@K) for targeted treatment of Alzheimer's disease (AD), effectively mitigating Aβ aggregate and alleviating neuroinflammation. Transcriptomics analysis revealed the therapeutic mechanism of PDA@K.
Review
Pharmacology & Pharmacy
Macarena Sanchez-Navarro, Ernest Giralt
Summary: The blood-brain barrier is important for limiting drug delivery to the brain, but it also plays a crucial role in nutrient entrance. Peptide shuttles offer a promising strategy for increasing drug transport across the blood-brain barrier by utilizing its natural transport mechanisms. In recent years, the field of peptide shuttles has significantly evolved, with various classifications and sources being explored.
Article
Biophysics
Stephanie Andrade, Maria C. Pereira, Joana A. Loureiro
Summary: Alzheimer's disease (AD) is an incurable neurological illness and the leading cause of dementia, characterized by amyloid beta (Aβ) fibril deposits. Caffeic acid (CA) has potential value for AD therapy due to its antiamyloidogenic, anti-inflammatory, and antioxidant properties. Liposomes loading CA were produced and Tf was conjugated to the liposomes' surface to direct the nanoparticles (NPs) to the blood-brain barrier. The optimized Tf-modified NPs exhibited suitable physical properties and encapsulation efficiency, and showed sustained release of CA for 8 days. The drug delivery system (DDS) can prevent Aβ aggregation and fibril formation, and disaggregate mature fibrils, indicating its potential for preventing and treating AD.
COLLOIDS AND SURFACES B-BIOINTERFACES
(2023)
Article
Toxicology
Guillaume Bianconi, Isabelle Malissin, Laurence Labat, Nihel Khoudour, Pascal Houze, Nicolas Pallet, Bruno Megarbane, Xavier Decleves
Summary: Tramadol poisoning in a kidney transplant patient resulted in marked and prolonged serotonin toxicity, attributed to increased production of M2 due to inhibition of tramadol metabolism by paroxetine and propranolol. This patient had normal CYP2D6-metabolizer status based on genotyping, but the metabolic profile revealed the impact of strong mechanism-based inhibitors on tramadol metabolism, leading to prolonged serotonin toxicity caused by elevated M2 levels.
CLINICAL TOXICOLOGY
(2022)
Letter
Toxicology
Bruno Megarbane, Lucie Chevillard, Nihel Khoudour, Xavier Decleves
CLINICAL TOXICOLOGY
(2022)
Article
Pharmacology & Pharmacy
Maria Smirnova, Laura Goracci, Gabriele Cruciani, Laetitia Federici, Xavier Decleves, Helene Chapy, Salvatore Cisternino
Summary: A computational approach was used to develop pharmacophore models for a drug/proton-antiporter, which successfully predicted known substrates and identified new candidates. The study provides valuable insights into the characterization and identification of substrates for this transporter, and has potential implications for designing drugs with improved ability to cross the blood-brain barrier.
Article
Toxicology
Alicja Puszkiel, Isabelle Malissin, Salvatore Cisternino, Nicolas Pallet, Xavier Decleves, Bruno Megarbane
Summary: This study investigated the mechanisms of toxicity in a case of massive tramadol ingestion. A female patient who ingested 9000 mg sustained-release tramadol developed severe brain injury. The study found that the plasma concentrations of tramadol and its metabolites were extremely high, and the elimination half-lives were prolonged, possibly involving cerebral vasospasm.
CLINICAL TOXICOLOGY
(2022)
Article
Substance Abuse
El-Hadi Zerdazi, Emmanuel Curis, Emily Karsinti, Romain Icick, Maeva Fortias, Philippe Batel, Olivier Cottencin, Cyrille Orizet, Aurelia Gay, Philippe Coeuru, Alice Deschenau, Philippe Lack, Delphine Moisan, Anne-Laure Pelissier-Alicot, Arnaud Plat, Jean-Baptiste Trabut, Isabelle Kousignian, Luana Boumendil, Eric Vicaut, Nathalie Prince, Jean-Louis Laplanche, Frank Bellivier, Jean-Pierre Lepine, Cynthia Marie-Claire, Georges Brousse, Florence Vorspan, Vanessa Bloch
Summary: This study finds that the occurrence and severity of cocaine-induced transient hallucinations (CIH) are two distinct phenotypes in cocaine users. Cocaine dependence, number of dependence criteria, and frequency of use during the worst period of misuse are significantly associated with the occurrence and severity of CIH.
DRUG AND ALCOHOL DEPENDENCE
(2022)
Article
Neurosciences
Nina Choublier, Meryam Taghi, Marie-Claude Menet, Morgane Le Gall, Johanna Bruce, Philippe Chafey, Francois Guillonneau, Amelie Moreau, Claire Denizot, Yannick Parmentier, Samir Nakib, Didier Borderie, Haniaa Bouzinba-Segard, Pierre-Olivier Couraud, Sandrine Bourdoulous, Xavier Decleves
Summary: In this study, the response of human cerebral microvascular ECs to laminar physiological shear stress was investigated. The results showed that shear stress induced ECs quiescence and provided strong protection for hCMEC/D3 cells, suggesting a similar effect on the BBB. These findings provide new insights on the response of microvascular brain ECs to shear stress and the importance of shear stress for optimizing in vitro BBB models.
FLUIDS AND BARRIERS OF THE CNS
(2022)
Review
Biochemistry & Molecular Biology
Blaise Pasquiers, Salih Benamara, Mathieu Felices, Laurent Nguyen, Xavier Decleves
Summary: This article discusses the growing interest in therapeutic monoclonal antibodies (mAbs) for various diseases, focusing on their complex pharmacokinetic profiles. It reviews the existing PK modeling approaches to translate mAbs PK from animal models to humans, ranging from empirical models to PBPK models. The emphasis is on population PK methods, linear PK aspects, and TMDD mechanisms of mAbs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Thomas Rodier, Alicja Puszkiel, Evelina Cardoso, David Balakirouchenane, Celine Narjoz, Jennifer Arrondeau, Vincent Fallet, Nihel Khoudour, Monia Guidi, Michel Vidal, Xavier Decleves, Chantal Csajka, Jerome Alexandre, Jacques Cadranel, Elizabeth Fabre, Marie Wislez, Francois Goldwasser, Benoit Blanchet
Summary: High interindividual variability in clinical response to EGFR inhibitors like osimertinib in NSCLC may be linked to plasma exposure variability. A retrospective analysis of 87 NSCLC patients receiving osimertinib found no significant relationship between exposure and toxicity, but suggested that high exposure to EGFR inhibitors could be associated with poorer survival in NSCLC patients. Data from a smaller cohort of NSCLC patients treated with erlotinib further supported this finding.
Article
Health Care Sciences & Services
Clement Delage, Lea Darnaud, Bruno Etain, Marina Vignes, Tu-Ky Ly, Alexia Frapsauce, Marc Veyrier, Marine Delavest, Emeline Marlinge, Vincent Hennion, Manon Meyrel, Aude Jacob, Margot Chouchana, Julie Smati, Guillaume Pataud, Nihel Khoudour, Jean-Eudes Fontan, Laurence Labat, Frank Bellivier, Celia Lloret-Linares, Xavier Decleves, Vanessa Bloch
Summary: This study analyzed the phenotypic assessments of CYP/P-gp activities over four years and found that this evaluation is important for optimizing pharmacotherapy in psychiatry. Therapeutic adjustments based on metabolic profiles were suggested, leading to improved treatment outcomes.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Panpan Ma, Johanne Seguin, Nhu Ky Ly, Luis Castillo Henriquez, Eva Plansart, Karim Hammad, Rabah Gahoual, Helene Dhotel, Charlotte Izabelle, Bruno Saubamea, Cyrille Richard, Virginie Escriou, Nathalie Mignet, Yohann Corvis
Summary: This study reports the formulation, stability, and in vitro efficiency of Fisetin nanocrystals stabilized by poloxamer P407. The nanocrystals exhibit uniform size and high stability in various environments, and show improved cytotoxicity and anti-angiogenic effect compared to the free drug, suggesting promising clinical applications.
INTERNATIONAL JOURNAL OF PHARMACEUTICS-X
(2022)
Article
Chemistry, Analytical
David Balakirouchenane, Axelle Vasseur, Fideline Bonnet-Serrano, Minna Choi, Nihel Khoudour, Alicja Puszkiel, Lionel Groussin, Michel Vidal, Xavier Decleves, Jerome Bertherat, Benoit Blanchet
Summary: A LC-MS/MS method was developed and validated for the quantification of ODT and MTP in human plasma. The method was accurate and precise, and can be used for plasma drug monitoring during the dose-titration period.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Pharmacology & Pharmacy
Lea Darnaud, Clement Delage, Youssef Daali, Anne-Priscille Trouvin, Serge Perrot, Nihel Khoudour, Nadia Merise, Laurence Labat, Bruno Etain, Frank Bellivier, Celia Lloret-Linares, Vanessa Bloch, Emmanuel Curis, Xavier Decleves
Summary: Drug-metabolizing enzymes and drug transporters play crucial roles in drug pharmacokinetics and response. The cocktail-based phenotyping approach involves administering multiple probe drugs to evaluate the activities of CYP and transporter simultaneously. This study determined the range of phenotyping indices in healthy volunteers and classified patients with therapeutic issues based on CYP and P-gp activities.
Article
Medicine, Research & Experimental
Shana O. Warner, Yufei Dai, Nicole Sheanon, Michael V. Yao, Rebecca L. Cason, Shahriar Arbabi, Shailendra B. Patel, Diana Lindquist, Jason J. Winnick
Summary: Fasting increases the risk of hypoglycemia in individuals with type 1 diabetes, and it also negatively affects insulin-induced hypoglycemia responses in healthy individuals.
Article
Pharmacology & Pharmacy
Blaise Pasquiers, Salih Benamara, Mathieu Felices, David Ternant, Xavier Decleves, Alicja Puszkiel
Summary: The objective of this study was to develop a generic physiologically based pharmacokinetic (PBPK) translational approach for monoclonal antibodies (mAb) using open-source software. The translation of bevacizumab was used as a case example to demonstrate the model. The predictions of the model were within an acceptable range for both area under the concentration-time curve (AUC) and maximum concentration (C-max).
Article
Oncology
Thibaud Derippe, Sylvain Fouliard, Ibtissam Marchiq, Sandra Dupouy, Maria Almena-Carrasco, Julia Geronimi, Xavier Decleves, Marylore Chenel, Donald E. Mager
Summary: A mechanistic pharmacokinetic/pharmacodynamic model has been developed to quantitatively support the beneficial impact of lymphodepletion before the infusion of allogeneic CAR-T cell products. Mediation through IL-7 increase and host T lymphocytes decrease is highlighted, and the model can be further used to optimize the lymphodepletion regimen in CAR-T cell therapies.
CANCER RESEARCH COMMUNICATIONS
(2022)
