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.
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
Geriatrics & Gerontology
Bruno Santos-Lima, Enrica Caterina Pietronigro, Eleonora Terrabuio, Elena Zenaro, Gabriela Constantin
Summary: Neutrophil migration plays a crucial role in the development of neurological diseases with inflammatory components. These cells can damage the blood-brain barrier and the blood-cerebrospinal fluid barrier, leading to significant tissue damage.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
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.
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
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
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
Virology
Eleanor M. Marshall, Marion P. G. Koopmans, Barry Rockx
Summary: This review focuses on the mechanisms of arboviral neuroinvasion, specifically on the haematogenous and transneural routes employed by flaviviruses. The gaps in knowledge regarding lesser-studied interfaces and novel routes are identified. The complex balance of pro-inflammatory and antiviral immune responses, particularly in the context of the hypothesized Trojan horse mechanism, is also discussed.
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
Xin-Yu Ma, Ting-Ting Yang, Lian Liu, Xiao-Chun Peng, Feng Qian, Feng-Ru Tang
Summary: The loss of neurons caused by progressive damage to the nervous system is proposed as the main pathogenesis of neurodegenerative diseases. Ependyma, composed of ciliated ependymal cells, plays a role in the formation of the brain-cerebrospinal fluid barrier (BCB) and the circulation and material exchange of cerebrospinal fluid (CSF) and brain interstitial fluid. Radiation-induced brain injury (RIBI) leads to impairments of the blood-brain barrier (BBB). The vulnerability of ependyma to immune responses may disrupt the integrity of BCB, affecting CSF flow and material exchange, and contributing to the pathogenesis of neurodegenerative diseases.
Review
Pharmacology & Pharmacy
Mariana Matias, Adriana O. O. Santos, Samuel Silvestre, Gilberto Alves
Summary: Epilepsy is a chronic and complex neurological disease affecting approximately 50 million people worldwide. Despite the introduction of numerous new antiseizure drugs, many patients still suffer from uncontrolled seizures, necessitating the development of more effective therapies. Nanomedicine offers a promising approach to deliver drugs to the brain, enhancing their therapeutic potential. This review addresses the general features and management of epilepsy, as well as the challenges in developing better antiseizure therapies. It also discusses the role of nanomedicines in selectively delivering drugs, overcoming physical-chemical limitations, improving brain penetration, reducing adverse effects, and circumventing drug resistance.
Article
Pharmacology & Pharmacy
Soraia Silva, Joana Bicker, Amilca Falcao, Ana Fortuna
Summary: The intranasal route is being explored for systemic drug delivery and treatment of pulmonary and neurological diseases. The air-liquid interface (ALI) method promotes cell differentiation and optimization of airway epithelium, providing relevant input for inhalation and pulmonary toxicology. However, there is currently no consensus on the validation of the ALI method, hampering data comparison.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Ivanna Hrynchak, Diana Cocioaba, Alexandra I. Fonseca, Radu Leonte, Sergio J. C. do Carmo, Roxana Cornoiu, Amilcar Falcao, Dana Niculae, Antero J. Abrunhosa
Summary: Antibody and nanobody-based copper-64 radiopharmaceuticals are proposed as theranostic tools in human diseases. This study discusses the production, purification, and radiolabeling of antibodies and nanobodies using copper-64 obtained from both solid and liquid targets. The liquid target method is practical and reliable, offering advantages such as speed, ease of automation, and continuous production.
Article
Chemistry, Multidisciplinary
Ana C. Goncalves, Ana R. Nunes, Sara Meirinho, Miguel Ayuso-Calles, Rocio Roca-Couso, Raul Rivas, Amilcar Falcao, Gilberto Alves, Luis R. Silva, Jose David Flores-Felix
Summary: This study analyzes the biological potential of blueberries and sweet cherries in several dimensions of human health, emphasizing the research on the benefits of consuming these fruits. Through the phenolic profile analysis of phenolic-enriched extracts from blueberries and sweet cherries, their antioxidant potential and ability to inhibit α-glucosidase enzyme activity were evaluated, along with their antimicrobial activity. The results demonstrate the significant antioxidant and antimicrobial properties of blueberries and sweet cherries, which are correlated with the presence of phenolic compounds.
APPLIED SCIENCES-BASEL
(2023)
Article
Pharmacology & Pharmacy
Rui Silva, Helena Colom, Joana Bicker, Anabela Almeida, Ana Silva, Francisco Sales, Isabel Santana, Amilcar Falcao, Ana Fortuna
Summary: This study aimed to develop a population pharmacokinetic (PopPK) model for perampanel in patients with refractory epilepsy. The results showed that a one-compartment model with first-order elimination best described the pharmacokinetic profiles of perampanel. Covariates such as enzyme-inducing antiepileptic drugs (EIAEDs) and body mass index (BMI) were found to significantly affect the clearance and volume of distribution of perampanel.
Article
Infectious Diseases
Maria Aquino, Maria Tinoco, Joana Bicker, Amilcar Falcao, Marilia Rocha, Ana Fortuna
Summary: Amikacin is the preferred antibiotic for treating Gram-negative infections in neutropenic oncology patients. However, there is a lack of population pharmacokinetic studies on amikacin in this patient population. This large-scale retrospective study investigated the effects of tumor diseases, chemotherapy, lag time, age, and renal function on amikacin pharmacokinetics in neutropenic cancer patients. The results showed that oncology patients received higher daily doses of amikacin and had increased drug clearance. Chemotherapy influenced amikacin pharmacokinetics and drug clearance decreased with longer lag time. The impact of aging on amikacin doses was stronger than chemotherapy. This research suggests that cancer patients may require higher initial doses of amikacin, especially within 30 days of starting chemotherapy.
Article
Biochemistry & Molecular Biology
Vanessa Brito, Mariana Marques, Marta Esteves, Catarina Serra-Almeida, Gilberto Alves, Paulo Almeida, Liliana Bernardino, Samuel Silvestre
Summary: Novel 16E-arylidene-5 alpha,6 alpha-epoxyepiandrosterone derivatives were synthesized and evaluated for their cytotoxicity and neuroprotective activity. Some of these compounds showed selective cytotoxic effects in tumoral cell lines with evidence of apoptosis activation. However, they did not demonstrate significant neuroprotection against 6-OHDA-induced neurotoxicity. Molecular docking simulations predicted a strong affinity between these compounds and 5 alpha-reductase and 17 alpha-hydroxylase-17,20-lyase enzymes.
Review
Chemistry, Medicinal
Ana R. R. Nunes, Elisabete C. C. Costa, Gilberto Alves, Luis R. Silva
Summary: Diabetes mellitus is a metabolic disease characterized by abnormal blood glucose levels caused by a lack of insulin secretion or impaired insulin action. The incidence of diabetes is increasing, resulting in high healthcare costs. Current drugs have side effects, leading to kidney and liver problems. Natural compounds rich in anthocyanidins have potential for the prevention and treatment of diabetes, but their application is hindered by issues such as lack of standardization and poor stability. Nanotechnology can be used for effective delivery of these compounds.
Review
Biochemistry & Molecular Biology
Jordi Olloquequi, Miren Ettcheto, Amanda Cano, Ana Fortuna, Joana Bicker, Elena Sanchez-Lopez, Cristian Paz, Jesus Urena, Ester Verdaguer, Carme Auladell, Antoni Camins
Summary: Licochalcone A (Lico-A) is a potential neuroprotective agent with various mechanisms of action, including enhancing cognitive activity, inhibiting neuroinflammation, reducing tau phosphorylation, increasing acetylcholine levels, decreasing amyloid plaques, and exerting antioxidant effects. Further research on the underlying mechanisms and targets of Lico-A may provide new insights for the treatment of cognitive disorders and neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Sara Meirinho, Marcio Rodrigues, Adriana O. Santos, Amilcar Falcao, Gilberto Alves
Summary: The intranasal administration of Perampanel (PER) through the olfactory pathway showed improved brain distribution and demonstrated anticonvulsant and anxiolytic effects in mice, indicating a potential alternative to oral treatment for epilepsy and anxiety. However, it also caused some neuromotor impairment, which was improved with repeated administrations. The study supports the design of clinical trials to evaluate the efficacy of intranasal PER delivery in treating neurological-related conditions.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Patricia Henriques, Joana Bicker, Soraia Silva, Slavomira Doktorovov, Ana Fortuna
Summary: In nasal drug product development, it is important to conduct screening studies to select promising compounds or formulations. The Parallel Artificial Membrane Permeability Assay (PAMPA) has been used to evaluate drug permeability across various barriers. This study optimized a new nasal-PAMPA model using a biorelevant medium with mucin, which accurately predicted nasal permeability and showed potential for drug and formulation screening.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Patricia C. Pires, Mariana Fernandes, Francisca Nina, Francisco Gama, Maria F. Gomes, Lina E. Rodrigues, Sara Meirinho, Samuel Silvestre, Gilberto Alves, Adriana O. Santos
Summary: The aim of this study was to develop a nanoemulsion (NE) with good solubilization capacity for lipophilic drugs and the ability to promote the absorption of drugs with low permeability. Compositions containing two lipids were screened and characterized, and one composition showed high droplet size homogeneity without the need for high energy methods. Optimized compositions containing a high proportion of propylene glycol monocaprylate NF were able to solubilize simvastatin at high drug strength and promote faster intranasal absorption of the hydrophilic prodrug fosphenytoin.
Article
Pharmacology & Pharmacy
Patricia Henriques, Joana Bicker, Andreia Carona, Margarida Miranda, Carla Vitorino, Slavomira Doktorovova, Ana Fortuna
Summary: This study investigated the application of amorphous solid dispersions (ASD) for nasal delivery, and compared two particle engineering strategies. The results showed that ASD with hydroxypropyl methylcellulose (HPMC) enhanced drug release and permeation, leading to fast drug absorption. In vitro release and ex vivo permeation studies were found to be predictive tools for nasal absorption.
JOURNAL OF PHARMACEUTICAL INVESTIGATION
(2023)
