Review
Pharmacology & Pharmacy
Chukwunonso K. Nwabufo, Reina Bendayan
Summary: The development of clinically effective drugs to complement existing vaccines is crucial for reducing the impact of COVID-19. This study examines how drug metabolism, transport, and inflammatory response may affect the efficacy of COVID-19 drugs, and provides expert opinions on strategies to improve their effectiveness.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2022)
Review
Multidisciplinary Sciences
Iman Imtiyaz Ahmed Juvale, Azzmer Azzar Abdul Hamid, Khairul Bariyyah Abd Halim, Ahmad Tarmizi Che Has
Summary: The multidrug resistance phenomenon poses a significant threat to the pharmaceutical industry and is mediated by multidrug transporters like P-glycoprotein. P-glycoprotein, with its versatile binding sites, accommodates various compounds and plays crucial roles in both multidrug resistant diseases and physiological functions in the human body.
Article
Pharmacology & Pharmacy
Chaitali Ghosh, Rosemary Westcott, Emilio Perucca, Mohammed Hossain, William Bingaman, Imad Najm
Summary: This study emphasizes for the first time the dependence of pro-apoptotic and anti-apoptotic protein levels on the CYP-mediated mechanism in polytherapy with antiseizure medications (ASMs), which regulates free radicals, cytotoxicity, and mitochondrial activity.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Sweilem B. Al Rihani, Lucy I. Darakjian, Malavika Deodhar, Pamela Dow, Jacques Turgeon, Veronique Michaud
Summary: The blood-brain barrier is crucial for regulating homeostasis in the central nervous system by controlling the entry of substances and supplying nutrients to the brain. Drug transporters at the BBB play a key role in determining drug distribution to the brain, and their expression and functionality can be influenced by inflammatory conditions and diseases. This can impact the efficacy and toxicity of drugs used to treat conditions such as Alzheimer's disease, epilepsy, and stroke.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Hanqing Chen, Shuang Zhou, Meilin Zhu, Bing Wang, Wei Chen, Lingna Zheng, Meng Wang, Weiyue Feng
Summary: The study reveals that PEI-GNPs have significant effects on hepatic drug-metabolic enzymes and de novo lipogenesis in mice, leading to liver inflammation and partial hepatotoxicity. Therefore, it is crucial to consider the interaction between nanomaterials and the liver and modify the surface chemistry of GNPs before biomedical application.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Nikola Pastvova, Petr Dolezel, Petr Mlejnek
Summary: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults with complex genetic alterations and protection from the blood-brain barrier (BBB). The study found that heat shock protein 90 (HSP90) inhibitors, GDN and 17-AAG, induced extensive cell death with apoptotic characteristics in glioma cell lines, regardless of genetic alterations. These inhibitors were weak substrates of ABCB1 and ABCG2, suggesting potential benefits for GBM patients.
Article
Infectious Diseases
Mu-Tong Fang, You-Feng Su, Hui-Ru An, Pei-Ze Zhang, Guo-Fang Deng, Hou-Ming Liu, Zhi Mao, Jian-Feng Zeng, Guobao Li, Qian-Ting Yang, Zhong-Yuan Wang
Summary: The main risk factor of RR/MDR-TBM is a history of anti-tuberculosis treatment. In our study, a linezolid-containing regimen appears to significantly lower the mortality rate of RR/MDR-TBM. Linezolid should be prospectively evaluated in the treatment of RR/MDR-TBM.
BMC INFECTIOUS DISEASES
(2021)
Article
Veterinary Sciences
Heidrun Potschka, Andrea Fischer, Wolfgang Loescher, Holger A. Volk
Summary: Drug resistance is a major issue in the treatment of canine epilepsies, affecting quality of life and survival. Human medicine research has shown that disease severity and pharmacokinetic changes contribute to antiseizure medication failure. In dogs, there is limited understanding of clinical patterns and mechanisms of drug-resistant epilepsy, but factors such as seizure density, genetic background, and epigenetic mechanisms may influence medication efficacy.
VETERINARY JOURNAL
(2023)
Article
Pharmacology & Pharmacy
Christine Wegler, Jacek R. Wisniewski, Ida Robertsen, Hege Christensen, Jens Kristoffer Hertel, Joran Hjelmesaeth, Rasmus Jansson-Lofmark, Anders Asberg, Tommy B. Andersson, Per Artursson
Summary: This study used global proteomics to characterize the protein composition of jejunum and liver in obese donors, revealing the expression of drug-metabolizing enzymes in the jejunum for the first time. The study also showed differences in enzyme expression between the liver and jejunum, indicating the role of the small intestine in drug metabolism. Additionally, the expression of these enzymes was not correlated with physiological factors and did not differ significantly between obese and non-obese donors.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Pharmacology & Pharmacy
Robert Hermann, Peter Krajcsi, Markus Fluck, Annick Seithel-Keuth, Afrim Bytyqi, Andrew Galazka, Alain Munafo
Summary: Cladribine is a drug used to treat patients with relapsing multiple sclerosis, which is phosphorylated in target cells to its active adenosine triphosphate form. The distribution of cladribine across biological membranes is facilitated by several uptake and efflux transporters, and it plays a role in intestinal absorption, distribution throughout the body, and intracellular uptake.
CLINICAL PHARMACOKINETICS
(2021)
Article
Veterinary Sciences
Andrea Fischer, Velia-Isabel Huelsmeyer, Viviana P. Munoz P. Schmieder, Andrea Tipold, Marion Kornberg, Florian Koenig, Felix K. Gesell, Liza K. Ahrend, Holger A. Volk, Heidrun Potschka
Summary: The efficacy and tolerability of COX-2 inhibitor add-on therapy in dogs with phenobarbital-resistant epilepsy were investigated in this study. Results showed that only a small number of dogs responded to the treatment, indicating that overall, this combination therapy is not significantly effective in overcoming epilepsy resistant to phenobarbital.
FRONTIERS IN VETERINARY SCIENCE
(2022)
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
Biochemistry & Molecular Biology
Rosemary Westcott, Natalie Chung, Arnab Ghosh, Lisa Ferguson, William Bingaman, Imad M. Najm, Chaitali Ghosh
Summary: This study reveals that the different isoforms of glucocorticoid receptor (GR) at the blood-brain barrier (BBB) play important roles in the pathogenesis of drug-resistant epilepsy with focal cortical dysplasia (FCD). The expression of GR beta is upregulated in dysplastic brain tissue and is associated with age and gender. The findings suggest that GR beta could serve as a potential biomarker and therapeutic target for dysplasia in epilepsy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Huilong Luo, Lucie Chevillard, Frank Bellivier, Bruno Megarbane, Bruno Etain, Salvatore Cisternino, Xavier Decleves
Summary: This article discusses the key role of brain barriers in the neuropharmacokinetics of lithium, revealing the heterogenous distribution of lithium in the brain and the variability in transport mechanisms through brain barriers, which may improve the understanding of PK-PD of lithium and its interindividual variability in drug response.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Patrick T. Ronaldson, Thomas P. Davis
Summary: Ischemic stroke is a major cause of morbidity and mortality globally. Despite positive results in preclinical studies, only one compound has advanced to Phase III clinical trial evaluation. This may be due to the neglect of transport mechanisms at the blood-brain barrier and neurovascular unit. This review highlights the role of BBB transporters in drug delivery and their expression in different brain cell types.
Article
Cardiac & Cardiovascular Systems
Helene David, Aurore Ughetto, Philippe Gaudard, Maelle Plawecki, Nitchawat Paiyabhroma, Emma Zub, Pascal Colson, Sylvain Richard, Nicola Marchi, Pierre Sicard
Summary: The study utilized in vivo photoacoustic imaging to track changes in vascular oxygen saturation in multiple organs and the brain post-myocardial infarction. Results showed a correlation between LV sO(2) and cardiac dysfunction, with global hypoxia observed in the brain, kidney, and liver shortly after MI, but returning to pre-MI levels after 7 days.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2021)
Article
Environmental Sciences
Isabel Forner-Piquer, Adele Faucherre, Julia Byram, Marine Blaquiere, Frederic de Bock, Laurence Gamet-Payrastre, Sandrine Ellero-Simatos, Etienne Audinat, Chris Jopling, Nicola Marchi
Summary: In zebrafish larvae, exposure to high concentrations of glyphosate leads to behavioral and neurophysiological defects, while cellular and transcript signatures can be detected in response to low doses.
Article
Environmental Sciences
Isabel Forner-Piquer, Wendy Klement, Giuseppe Gangarossa, Emma Zub, Frederic de Bock, Marine Blaquiere, Tangui Maurice, Etienne Audinat, Adele Faucherre, Frederic Lasserre, Sandrine Ellero-Simatos, Laurence Gamet-Payrastre, Chris Jopling, Nicola Marchi
Summary: The study found that male offspring of mice exposed to a pesticide cocktail exhibited anxiety-like behavior, while zebrafish larvae exposed to the pesticide cocktail during development showed alterations in motor behaviors.
ENVIRONMENTAL POLLUTION
(2021)
Article
Clinical Neurology
Martina Di Nunzio, Rossella Di Sapia, Diletta Sorrentino, Valentina Kebede, Milica Cerovic, Giorgia S. Gullotta, Marco Bacigaluppi, Etienne Audinat, Nicola Marchi, Teresa Ravizza, Annamaria Vezzani
Summary: Microgliosis, characterized by microglia proliferation, plays different roles in acquired epilepsy, contributing to neurodegeneration in the early phase and seizures in chronic disease. Pharmacological intervention targeting microglia proliferation may hold promise for improving disease outcomes.
Article
Sport Sciences
Thomas S. Owens, Thomas A. Calverley, Benjamin S. Stacey, George Rose, Lewis Fall, Hayato Tsukamoto, Gareth Jones, Robin Corkill, Edouard Tuaillon, Christophe Hirtz, Sylvain Lehmann, Nicola Marchi, Christopher J. Marley, Damian M. Bailey
Summary: This study found that in rugby union players, prior recurrent contact and concussion history is associated with accelerated cognitive decline, potentially through free radical-mediated suppression of CVR and neuronal injury.
SCANDINAVIAN JOURNAL OF MEDICINE & SCIENCE IN SPORTS
(2021)
Article
Endocrinology & Metabolism
Damian M. Bailey, Anthony R. Bain, Ryan L. Hoiland, Otto F. Barak, Ivan Drvis, Christophe Hirtz, Sylvain Lehmann, Nicola Marchi, Damir Janigro, David B. MacLeod, Philip N. Ainslie, Zeljko Dujic
Summary: In this study, it was found that prolonged apnea duration during voluntary asphyxia leads to increased cerebral blood flow and blood-brain barrier permeability. The study highlights the critical role of hypoxemia and hypercapnia in BBB disruption.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Article
Endocrinology & Metabolism
Geoffrey Canet, Charleine Zussy, Celia Hernandez, Nathalie Chevallier, Nicola Marchi, Catherine Desrumaux, Laurent Givalois
Summary: This study reveals that chronic corticosterone (CORT) consumption is a main risk factor for Alzheimer's disease (AD) and suggests that glucocorticoid-based therapies should be prescribed with caution in populations with AD risk.
NEUROENDOCRINOLOGY
(2022)
Review
Clinical Neurology
Erwin A. van Vliet, Nicola Marchi
Summary: The neurovascular unit (NVU) is a complex network involving different cells in the brain, including specialized brain endothelium, glial and mural cells, and neurons. Research suggests that dysfunction of the NVU is a common mechanism underlying late-onset seizures or epilepsy, neurological and neurodegenerative disorders associated with aging. Further studies also indicate that seizure activity may contribute to brain aging by causing regional NVU dysfunction, while cerebrovascular pathology may be linked to comorbidities. Diagnostic approaches tailored to seizure conditions in the elderly and disease-modifying strategies focusing on NVU restoration and control of inflammation are being explored. However, there are still knowledge gaps and clinical challenges in understanding seizure onset and conditions in an aging population.
Article
Clinical Neurology
Geoffrey Canet, Emma Zub, Charleine Zussy, Celia Hernandez, Marine Blaquiere, Valentin Garcia, Mathieu Vitalis, Frederic DeBock, Maria Moreno-Montano, Etienne Audinat, Catherine Desrumaux, Emmanuel Planel, Laurent Givalois, Nicola Marchi
Article
Critical Care Medicine
Charlotte Oris, Julie Durif, Marion Rouzaire, Bruno Pereira, Damien Bouvier, Samy Kahouadji, Mathieu Abbot, Marina Brailova, Sylvain Lehmann, Christophe Hirtz, Philippe Decq, Bernard Dusfour, Nicola Marchi, Vincent Sapin
Summary: This study evaluated the use of seven blood biomarkers for sport-related concussions. Only S100B and GFAP remained stable over the course of a season. The individual percentage change of S100B and NFL concentrations measured 36 hours after concussion was significantly different between non-resolutive and resolutive cases.
JOURNAL OF NEUROTRAUMA
(2023)
Article
Clinical Neurology
N. Cresto, A. Janvier, N. Marchi
Summary: While seizures involve neuronal events, other brain cells also play a significant role in synaptic transmission. The blood-brain barrier and neuro-glio-vascular unit regulate the brain's homeostasis by maintaining the composition of the interstitial fluid. Damage to the blood-brain barrier and neuroinflammation are mechanisms that sustain abnormal neuronal discharges, which are associated with various pathological conditions. The understanding of the role of the blood-brain barrier and neuroinflammation in epilepsy could lead to the development of biomarkers for predicting disease progression and the discovery of new diagnostic and therapeutic approaches.
REVUE NEUROLOGIQUE
(2023)
Article
Environmental Sciences
Sophie Sakkaki, Noemie Cresto, Raphael Chancel, Emma Zub, Pierre Sicard, Tangui Maurice, Sandrine Ellero-Simatos, Laurence Gamet-Payrastre, Nicola Marchi, Julie Perroy
Summary: This study investigates the risk of continuous exposure to glyphosate from prenatal to adulthood and the impact of Shank3 synaptic gene mutation on neurological adaptations. The results show that prenatal exposure to glyphosate increases embryonic mortality rate and leads to neuroinflammation and behavioral adaptations in progenies of Shank3(Delta C/+) mice.
ENVIRONMENT INTERNATIONAL
(2023)
Article
Neurosciences
Valentin Garcia, Marine Blaquiere, Alicia Janvier, Noemie Cresto, Carla Lana, Athenais Genin, Helene Hirbec, Etienne Audinat, Adele Faucherre, Emmanuel L. Barbier, Sophie Hamelin, Philippe Kahane, Chris Jopling, Nicola Marchi
Summary: This study reveals the association between mechanosensitive channel PIEZO1 and inflammatory responses in the central nervous system, particularly in the context of epilepsy. The expression of PIEZO1 is increased in epileptogenic regions of the brain and correlates with pro-inflammatory biomarkers. Additionally, TNF alpha is identified as a direct regulator of PIEZO1 expression. These findings highlight the potential significance of PIEZO1 in neuro-inflammatory processes.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Cell Biology
Fabiana Oliviero, Wendy Klement, Lucile Mary, Yannick Dauwe, Yannick Lippi, Claire Naylies, Veronique Gayrard, Nicola Marchi, Laila Mselli-Lakhal
Summary: Non-Alcoholic Fatty Liver Disease (NAFLD) is a common chronic liver disease, especially in obese individuals. This study suggests that the nuclear receptor CAR may play a role in the pathogenesis of NAFLD and could be a potential therapeutic target. In mice, deletion of CAR led to a NASH-like hepatic transcriptomic signature and astrogliosis in the hypothalamus of female mice.
Article
Immunology
Anais Virenque, Hennariikka Koivisto, Salli Antila, Emma Zub, Erin Jane Rooney, Diana Miszczuk, Adrian Mueller, Enija Stoka, Nicola Marchi, Kari Alitalo, Heikki Tanila, Francesco Mattia Noe
Summary: Understanding the pathological mechanisms of chronic traumatic brain injury (TBI) could lead to new therapeutic approaches. This study examined the role of meningeal lymphatic vessel dysfunction in modifying post-TBI pathology. The results showed that preexisting dysfunction of meningeal lymphatic vessels did not impact the structural brain damage and post-TBI behavior, but was associated with increased activation of microglia over time.
BRAIN, BEHAVIOR, & IMMUNITY - HEALTH
(2022)
