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)
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)
Review
Physiology
Jeff F. Dunn, Albert M. Isaacs
Summary: The blood-brain barrier, blood-cerebrospinal fluid barrier, and CSF-brain barriers are crucial for regulating the separation of nerves and glia from blood and CSF in the central nervous system. Hypoxia and inflammation can disrupt these barriers, impacting the overall health of the nervous system.
JOURNAL OF APPLIED PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Natalia Czarniak, Joanna Kaminska, Joanna Matowicka-Karna, Olga Martyna Koper-Lenkiewicz
Summary: Cerebrospinal fluid plays a crucial role in protecting the central nervous system by providing support, absorbing shocks, and transporting nutrients and waste products. This review provides an overview of cerebrospinal fluid history, production, circulation, main components, and the roles of blood-brain barrier and blood-cerebrospinal fluid barrier in maintaining homeostasis. The utility of Albumin Quotient evaluation in the diagnosis of CNS diseases is discussed. The importance of research on cerebrospinal fluid for improving disease management and discovering new treatment options is highlighted.
Review
Nutrition & Dietetics
Shannon Morgan McCabe, Ningning Zhao
Summary: Manganese is an essential trace nutrient for life, but can become neurotoxic at high concentrations in the brain. The brain consists of two barriers - the blood-brain barrier (BBB) formed by endothelial cells and the blood-CSF barrier (BCB) formed by the choroid plexus - that prevent substances in the systemic circulation from reaching the brain and spinal cord. Studies have provided insights into manganese transport and metabolism in the brain, with a focus on the roles of the BBB and BCB in maintaining brain manganese homeostasis.
Article
Oncology
Mohamed Badawi, Rajeev Menon, Andrew E. Place, Tammy Palenski, Gauri Sunkersett, Richard Arrendale, Rong Deng, Sara M. Federico, Todd M. Cooper, Ahmed Hamed Salem
Summary: Infiltration of malignant cells into the central nervous system is associated with poor clinical outcomes in hematological malignancies. Limited investigations have been conducted on the penetration of venetoclax into the central nervous system. This study demonstrates the ability of venetoclax to cross into the central nervous system and provides evidence of its potential role in improving clinical outcomes for patients with CNS complications.
Article
Clinical Neurology
Piergiorgio Grillo, Giulia Maria Sancesario, Davide Mascioli, Lorenza Geusa, Henri Zenuni, Emilia Giannella, David Della Morte, Nicola Biagio Mercuri, Tommaso Schirinzi
Summary: Prodromal constipation at Parkinson's disease onset may indicate a distinct neurodegenerative trajectory. Patients with prodromal constipation have more severe motor impairment at diagnosis and possible blood brain barrier disruption, requiring greater dopaminergic treatment in the mid-term. Conversely, patients without prodromal constipation exhibit prominent fatigue and pronounced central synucleinopathy.
PARKINSONISM & RELATED DISORDERS
(2022)
Article
Pharmacology & Pharmacy
Xiande Wang, Cheng Wu, Shiming Liu, Deqing Peng
Summary: Brain cancer is a highly aggressive cancer with limitations in current treatment strategies. The blood-brain barrier and blood-cerebrospinal fluid barrier pose additional challenges in drug delivery to brain tumors. Dual-targeting strategies have shown promise in enhancing drug delivery efficiency and targeting of tumor cells in brain tumors.
Article
Neurosciences
Yasuhiro Ogawa, Seioh Ezaki, Nobutake Shimojo, Satoru Kawano
Summary: The patient presented with various clinical symptoms of sepsis and after diagnosis and treatment, the orexin levels in the cerebrospinal fluid gradually recovered. This case provides new insights into the pathophysiology of sepsis-associated encephalopathy.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Immunology
Sarinnapha M. Vasunilashorn, Long H. Ngo, Simon T. Dillon, Tamara G. Fong, Becky C. Carlyle, Pia Kivisakk, Bianca A. Trombetta, Kamen V. Vlassakov, Lisa J. Kunze, Steven E. Arnold, Zhongcong Xie, Sharon K. Inouye, Towia A. Libermann, Edward R. Marcantonio
Summary: In a study of older adults undergoing hip or knee surgery, it was found that surgery did not compromise the blood-brain barrier integrity. After surgery, there was a higher correlation between plasma and CSF levels of CRP and IL-6, with an increase in all three inflammatory markers from preoperative to postoperative 1 month.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Immunology
Ronald J. Ellis, Scott Peterson, Mariana Cherner, Erin Morgan, Rachel Schrier, Bin Tang, Martin Hoenigl, Scott Letendre, Jenny Iudicello
Summary: This study suggests that cannabis may have a beneficial impact on HIV-associated blood-brain barrier (BBB) injury, with worse BBB index values correlated with higher levels of neural injury in cerebrospinal fluid (CSF). The findings support a potential therapeutic role of cannabis among people living with HIV (PWH) and may have important treatment implications for antiretroviral therapy (ART) effectiveness and toxicity.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Psychiatry
Rose Jeppesen, Sonja Orlovska-Waast, Nina Vindegaard Sorensen, Rune Haubo Bojesen Christensen, Michael Eriksen Benros
Summary: Neuroinflammation and blood-brain barrier dysfunction are commonly observed in patients with psychotic disorders. This study found that patients with psychotic disorders had increased blood-brain barrier permeability, higher levels of white blood cells in cerebrospinal fluid, and increased peripheral inflammation in inpatients.
SCHIZOPHRENIA BULLETIN
(2022)
Review
Immunology
Josephine A. Mapunda, Houyam Tibar, Wafa Regragui, Britta Engelhardt
Summary: Multiple Sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system (CNS), with varying prevalence worldwide. Understanding how immune cells enter the CNS and the effects of immunomodulatory treatments on neuroinflammation is crucial. The brain barriers play a key role in regulating immune cell entry into the CNS.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Bikram Khadka, Jae-Young Lee, Eui Kyun Park, Ki-Taek Kim, Jong-Sup Bae
Summary: Natural compounds can interact with drugs during the treatment of brain disorders, affecting the pharmacokinetic properties and cellular transport of drugs, potentially leading to synergistic toxicity or impeding drug interactions. Challenges arising from these natural compound-drug interactions and recent research approaches are discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Alexei Verkhratsky, Augustas Pivoriuas
Summary: The nervous system is protected and separated from the body by a complex system of barriers. In the central nervous system (CNS), these barriers include the blood-brain barrier and blood-spinal cord barrier, the arachnoid blood-cerebrospinal fluid barrier, the blood-cerebrospinal barrier of circumventricular organs, and the choroid plexus blood-cerebrospinal fluid barrier. In the peripheral nervous system, the barrier is maintained by tight junctions between specialized glial cells known as perineural cells. Astroglia contribute to all barriers in the CNS, and their dysfunction can compromise the integrity of these barriers.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Neurosciences
Javier Blesa, Guglielmo Foffani, Benjamin Dehay, Erwan Bezard, Jose A. Obeso
Summary: The prevailing theory of Parkinson disease pathogenesis involves the spread of alpha-synuclein toxicity from the periphery to the brain. While this bottom-up mechanism is implicated, early neuronal loss in the nigrostriatal system also plays a prominent role.
NATURE REVIEWS NEUROSCIENCE
(2022)
Article
Neurosciences
Salvatore Novello, Daniela Mercatelli, Federica Albanese, Chiara Domenicale, Alberto Brugnoli, Elisabetta D'Aversa, Silvia Vantaggiato, Sandra Dovero, Valentina Murtaj, Luca Presotto, Monica Borgatti, Derya R. Shimshek, Erwan Bezard, Rosa Maria Moresco, Sara Belloli, Michele Morari
Summary: The G2019S mutation of LRRK2 increases the risk of idiopathic Parkinson's disease and enhances susceptibility to environmental toxins through increased kinase activity. LRRK2 kinase inhibitors have neuroprotective effects in a mouse model.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Erwan Bezard
Summary: This opinion paper addresses the issue of conceptual sloppiness and poor methodological characterization in Parkinson's disease research, emphasizing its negative impact on progress and proposing a remedy.
Article
Neurosciences
Florent Laferriere, Stephane Claverol, Erwan Bezard, Francesca De Giorgi, Francois Ichas
Summary: The principal component of Lewy bodies and glial cytoplasmic inclusions is aggregated alpha-synuclein, and the inclusion bodies may cause cell death through the sequestration of partner proteins and organelles. Furthermore, the study found that the sarkosyl-insoluble proteomes of Parkinson's disease and multiple system atrophy have a significant overlap, consisting mainly of mitochondrial and neuronal synaptic proteins. Other fibrillization-prone proteins possibly cross-seeded by alpha-syn are not found in these extracts.
NPJ PARKINSONS DISEASE
(2022)
Article
Cell Biology
Marie-Laure Arotcarena, Federico N. Soria, Anthony Cunha, Evelyne Doudnikoff, Geoffrey Prevot, Jonathan Daniel, Mireille Blanchard-Desce, Philippe Barthelemy, Erwan Bezard, Sylvie Crauste-Manciet, Benjamin Dehay
Summary: Researchers have discovered that acidic nanoparticles can improve neurodegeneration and restore lysosomal function in Parkinson's disease, offering a new treatment strategy for this and other age-related proteinopathies.
Article
Clinical Neurology
Margaux Teil, Sandra Dovero, Mathieu Bourdenx, Marie-Laure Arotcarena, Sandrine Camus, Gregory Porras, Marie-Laure Thiolat, Ines Trigo-Damas, Celine Perier, Cristina Estrada, Nuria Garcia-Carrillo, Michele Morari, Wassilios G. Meissner, Maria Trinidad Herrero, Miquel Vila, Jose A. Obeso, Erwan Bezard, Benjamin Dehay
Summary: Synucleinopathies, including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, are characterized by the deposit of alpha-synuclein aggregates in neurons and glial cells. A study found that inoculating brain fractions containing glial cytoplasmic inclusions from multiple system atrophy patients into non-human primates resulted in neurodegeneration, oligodendrocyte loss, demyelination, neuroinflammation and alpha-synuclein pathology. These findings suggest the potential use of this experimental model for multiple system atrophy research and therapy development.
Article
Clinical Neurology
Leyre Merino-Galan, Haritz Jimenez-Urbieta, Marta Zamarbide, Tatiana Rodriguez-Chinchilla, Arantzazu Belloso-Iguerategui, Enrique Santamaria, Joaquin Fernandez-Irigoyen, Ana Aiastui, Evelyne Doudnikoff, Erwan Bezard, Alberto Ouro, Shira Knafo, Belen Gago, Ana Quiroga-Varela, Maria Cruz Rodriguez-Oroz
Summary: In Parkinson's disease, synaptic impairment may occur before neuronal degeneration. By studying a rat model, we found that synaptic energetic failure and accumulation of dysfunctional organelles are the earliest events that happen at dopaminergic terminals, preceding structural changes and cell death. We also identified key proteins involved in these earliest functional abnormalities, which could be targeted for therapeutic interventions to delay or prevent the development of Parkinson's disease.
Article
Biochemistry & Molecular Biology
Francesca De Giorgi, Muhammed Bilal Abdul-Shukkoor, Marianna Kashyrina, Leslie-Ann Largitte, Francesco De Nuccio, Brice Kauffmann, Alons Lends, Florent Laferriere, Sebastien Bonhommeau, Dario Domenico Lofrumento, Luc Bousset, Erwan Bezard, Thierry Buffeteau, Antoine Loquet, Francois Ichas
Summary: The distinct neuropathological features and inclusion bodies in different alpha-Synucleinopathies reflect the strain diversity of invasive alpha-Syn amyloids. However, the contribution of non-amyloid factors to specific diseases is still uncertain. In Multiple System Atrophy, alpha-Syn inclusions in oligodendrocytes seem to result from the storage of amyloid aggregates pre-assembled in neurons. These inclusions originate from unique molecular properties or other factors dysregulated in MSA.
Article
Neurosciences
Heather Hulme, Elva Fridjonsdottir, Theodosia Vallianatou, Reza Shariatgorji, Anna Nilsson, Qin Li, Erwan Bezard, Per E. Andren
Summary: L-DOPA administration is the primary treatment for Parkinson's disease, but long-term use can cause a hyperkinetic side-effect called L-DOPA-induced dyskinesia. The severity of dyskinesia is correlated with the levels of specific abnormally processed peptides, such as des-tyrosine dynorphins, substance P (1-7), and substance P (1-9). The levels of active neuropeptides are associated with the concentration of L-DOPA in the putamen, while truncated neuropeptides are correlated with dyskinesia severity.
NPJ PARKINSONS DISEASE
(2022)
Article
Clinical Neurology
Morgane Darricau, Taxiarchis Katsinelos, Flavio Raschella, Tomislav Milekovic, Louis Crochemore, Qin Li, Gregoire Courtine, William A. McEwan, Benjamin Dehay, Erwan Bezard, Vincent Planche
Summary: This study demonstrates that progressive supranuclear palsy (PSP) patient-derived tau aggregates can induce motor and behavioral impairments in non-human primates, showing characteristics of prion-like seeding and spreading of PSP lesions. This pilot study paves the way for using PSP tau-injected macaques as a relevant animal model to accelerate drug development for this rare and fatal neurodegenerative disease.
Review
Neurosciences
Juan Estaun-Panzano, Marie-Laure Arotcarena, Erwan Bezard
Summary: Synucleinopathies are a group of diseases characterized by the misfolding and aggregation of alpha-synuclein, leading to the formation of Lewy bodies. Studying the aggregation of alpha-synuclein is crucial for understanding these diseases, and recent breakthroughs have provided new insights into their mechanisms.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Neurosciences
Erwan Bezard, David Gray, Rouba Kozak, Matthew Leoni, Cari Combs, Sridhar Duvvuri
Summary: Currently available therapeutics for PD do not provide sustained and predictable relief from motor symptoms without significant adverse events (AEs). There is a need for a treatment that can effectively relieve motor symptoms with reduced risk of AEs.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2023)
Article
Biochemical Research Methods
Ibrahim Kaya, Luke S. Schembri, Anna Nilsson, Reza Shariatgorji, Sooraj Baijnath, Xiaoqun Zhang, Erwan Bezard, Per Svenningsson, Luke R. Odell, Per E. Andren
Summary: This study presents an on-tissue chemical derivatization MALDI mass spectrometry imaging approach for the comprehensive mapping of carboxyls and aldehydes in brain tissue sections. The approach successfully detected and imaged various carboxyl and aldehyde-containing endogenous metabolites simultaneously. The methodology provides a powerful tool for sensitive and simultaneous spatial molecular imaging of numerous aldehydes and carboxylic acids during pathological states in brain tissue.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Article
Clinical Neurology
Miguel Lopez-Cuina, Paul Guerin, Nathalie Dutheil, Christelle Martin, Thierry Leste Lasserre, Pierre-Olivier Fernagut, Wassilios G. Meissner, Erwan Bezard
Summary: This study demonstrates that lowering brain GRK2 levels through delivery of a GRK2-specific miRNA can reverse central nervous system insulin resistance and provide neuroprotection in a mouse model of multiple system atrophy. These findings suggest that GRK2 may be a potential therapeutic target for the treatment of MSA.
MOVEMENT DISORDERS
(2023)
Article
Neurosciences
Ibrahim Kaya, Anna Nilsson, Dominika Luptakova, Yachao He, Theodosia Vallianatou, Patrik Bjarterot, Per Svenningsson, Erwan Bezard, Per E. Andren
Summary: Metabolism of MPTP leads to the neurotoxin MPP+, which causes Parkinson's disease-like symptoms by destroying dopaminergic neurons in the brain. This study used mass spectrometry imaging to analyze glycerophospholipids and sphingolipids in monkey brains and found dysregulation of sulfatide metabolism in the MPTP-lesioned brain regions. Depletion of long-chain hydroxylated sulfatides suggests oxidative stress and damage to myelin in these regions. These findings contribute to our understanding of the molecular pathology of MPTP-induced parkinsonism and provide a basis for further research on dysregulated sulfatide metabolism in Parkinson's disease.
NPJ PARKINSONS DISEASE
(2023)
