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Blood brain barrier

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https://www.readbyqxmd.com/read/28339310/investigations-of-octylglyceryl-dextran-graft-poly-lactic-acid-nanoparticles-for-peptide-delivery-to-the-brain
#1
Asme Boussahel, Daniel M Ibegbu, Rhita Lamtahri, Julie Maucotel, Julien Chuquet, Benjamin Lefranc, Jérôme Leprince, Marta Roldo, Jean-Claude Le Mével, Darek Gorecki, Eugen Barbu
AIM: Develop modified dextran nanoparticles showing potential to assist with drug permeation across the blood-brain barrier for the delivery of neuropeptides. METHODS: Nanoparticles loaded by emulsification with model macromolecular actives were characterized in terms of stability, cytotoxicity and drug-release behavior. Peptide-loaded nanoformulations were tested in an in vivo trout model and in food-deprived mice. RESULTS: Nanoformulations loaded with model peptides showed good stability and appeared nontoxic in low concentration against human brain endothelial cells...
March 24, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28335421/pamam-dendrimers-cross-the-blood-brain-barrier-when-administered-through-the-carotid-artery-in-c57bl-6j-mice
#2
Bhairavi Srinageshwar, Sarah Peruzzaro, Melissa Andrews, Kayla Johnson, Allison Hietpas, Brittany Clark, Crystal McGuire, Eric Petersen, Jordyn Kippe, Andrew Stewart, Olivia Lossia, Abeer Al-Gharaibeh, Aaron Antcliff, Rebecca Culver, Douglas Swanson, Gary Dunbar, Ajit Sharma, Julien Rossignol
Drug delivery into the central nervous system (CNS) is challenging due to the blood-brain barrier (BBB) and drug delivery into the brain overcoming the BBB can be achieved using nanoparticles such as dendrimers. The conventional cationic dendrimers used are highly toxic. Therefore, the present study investigates the role of novel mixed surface dendrimers, which have potentially less toxicity and can cross the BBB when administered through the carotid artery in mice. In vitro experiments investigated the uptake of amine dendrimers (G1-NH₂ and G4-NH₂) and novel dendrimers (G1-90/10 and G4-90/10) by primary cortical cultures...
March 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28334978/therapeutic-window-of-dopamine-d2-3-receptor-occupancy-to-treat-psychosis-in-alzheimer-s-disease
#3
Suzanne Reeves, Emma McLachlan, Julie Bertrand, Fabrizia D Antonio, Stuart Brownings, Akshay Nair, Suki Greaves, Alan Smith, David Taylor, Joel Dunn, Paul Marsden, Robert Kessler, Robert Howard
Antipsychotic drugs, originally developed to treat schizophrenia, are used to treat psychosis, agitation and aggression in Alzheimer's disease. In the absence of dopamine D2/3 receptor occupancy data to inform antipsychotic prescribing for psychosis in Alzheimer's disease, the mechanisms underpinning antipsychotic efficacy and side effects are poorly understood. This study used a population approach to investigate the relationship between amisulpride blood concentration and central D2/3 occupancy in older people with Alzheimer's disease by combining: (i) pharmacokinetic data (280 venous samples) from a phase I single (50 mg) dose study in healthy older people (n = 20, 65-79 years); (ii) pharmacokinetic, 18F-fallypride D2/3 receptor imaging and clinical outcome data on patients with Alzheimer's disease who were prescribed amisulpride (25-75 mg daily) to treat psychosis as part of an open study (n = 28; 69-92 years; 41 blood samples, five pretreatment scans, 19 post-treatment scans); and (iii) 18F-fallypride imaging of an antipsychotic free Alzheimer's disease control group (n = 10, 78-92 years), to provide additional pretreatment data...
February 4, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334198/molecular-mechanisms-involved-in-the-interaction-of-neisseria-meningitidis-with-cells-of-the-human-blood-cerebrospinal-fluid-barrier
#4
Alexandra Schubert-Unkmeir
Neisseria meningitidis is one of the most common aetiological agents of bacterial meningitis, affecting predominantly children and young adults. The interaction of N. meningitidis with human endothelial cells lining blood vessels of the blood-cerebrospinal-fluid barrier (B-CSFB) is critical for meningitis development. In recent decades, there has been a significant increase in understanding of the molecular mechanisms involved in the interaction of N. meningitidis with brain vascular cells. In this review, we will describe how N...
March 3, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28334103/neuronal-and-peripheral-pentraxins-modify-glutamate-release-and-may-interact-in-blood-brain-barrier-failure
#5
Damian M Cummings, Tiffanie A Benway, Hinze Ho, Angelo Tedoldi, Monica M Fernandes Freitas, Lion Shahab, Christina E Murray, Angela Richard-Loendt, Sebastian Brandner, Tammaryn Lashley, Dervis A Salih, Frances A Edwards
Neuronal pentraxin 1 (NPTX1) has been implicated in Alzheimer's disease, being present in and around dystrophic neurons in plaques, affecting glutamatergic transmission postsynaptically and mediating effects of amyloidβ. Here, we confirm the presence of NPTX1 around plaques in postmortem Alzheimer's disease brain and report that acutely applied human NPTX1 increases paired-pulse ratio at mouse CA3-CA1 hippocampal synapses, indicating a decrease in glutamate release. In contrast, chronic exposure to NPTX1, NPTX2, or NPTX receptor decreases paired-pulse ratio, mimicking some of the earliest changes in mice expressing familial Alzheimer's disease genes...
February 23, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28332439/use-of-biopartitioning-micellar-chromatography-and-rp-hplc-for-the-determination-of-blood-brain-barrier-penetration-of-%C3%AE-adrenergic-imidazoline-receptor-ligands-and-qspr-analysis
#6
J Vucicevic, M Popovic, K Nikolic, S Filipic, D Obradovic, D Agbaba
For this study, 31 compounds, including 16 imidazoline/α-adrenergic receptor (IRs/α-ARs) ligands and 15 central nervous system (CNS) drugs, were characterized in terms of the retention factors (k) obtained using biopartitioning micellar and classical reversed phase chromatography (log kBMC and log kwRP, respectively). Based on the retention factor (log kwRP) and slope of the linear curve (S) the isocratic parameter (φ0) was calculated. Obtained retention factors were correlated with experimental log BB values for the group of examined compounds...
March 2017: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/28331318/surface-modified-gatifloxacin-nanoparticles-with-potential-for-treating-central-nervous-system-tuberculosis
#7
Patricia Marcianes, Sofia Negro, Luis García-García, Consuelo Montejo, Emilia Barcia, Ana Fernández-Carballido
A new nanocarrier is developed for the passage of gatifloxacin through the blood-brain barrier to treat central nervous system tuberculosis. Gatifloxacin nanoparticles were prepared by nanoprecipitation using poly(lactic-co-glycolic acid) (PLGA) 502 and polysorbate 80 or Labrafil as surface modifiers. The evaluation of in vivo blood-brain barrier transport was carried out in male Wistar rats using rhodamine-loaded PLGA nanoparticles prepared with and without the surface modifiers. At 30 and 60 minutes after administration, nanoparticle biodistribution into the brain (hippocampus and cortex), lungs, and liver was studied...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28330845/transport-across-the-choroid-plexus-epithelium
#8
Jeppe Praetorius, Helle Hasager Damkier
The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance...
March 22, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28327595/x-linked-inhibitor-of-apoptosis-inhibits-apoptosis-and-preserves-the-blood-brain-barrier-after-experimental-subarachnoid-hemorrhage
#9
Cheng Gao, Hongwei Yu, Cong Yan, Wenyang Zhao, Yao Liu, Dongdong Zhang, Jingwei Li, Nan Liu
Early brain injury following subarachnoid hemorrhage (SAH) strongly determines the prognosis of patients suffering from an aneurysm rupture, and apoptosis is associated with early brain injury after SAH. This study was designed to explore the role of X-linked inhibitor of apoptosis (XIAP) in early brain injury following SAH. The expression of XIAP was detected using western blotting and real-time RT-PCR in an autologous blood injection model of SAH. We also studied the role of XIAP in early brain injury and detected apoptosis-related proteins...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326470/targeted-treatment-of-brain-metastases
#10
REVIEW
Nicole Shonka, Vyshak Alva Venur, Manmeet S Ahluwalia
PURPOSE OF REVIEW: Brain metastases are the most common intracranial tumors in adults. Historically, the median survival after the diagnosis of brain metastases has been dismal and medical therapies had a limited role in the management of these patients. RECENT FINDINGS: The advent of targeted therapy has ushered in an era of increased hope for patients with brain metastases. The most common malignancies that result in brain metastases-melanoma, lung cancer, and breast cancer, often have actionable mutations, which make them good candidates for targeted systemic therapy...
April 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28326151/chronic-porphyromonas-gingivalis-infection-accelerates-the-occurrence-of-age-related-granules-in-apoe-mice-brains
#11
Sim K Singhrao, Sasanka Chukkapalli, Sophie Poole, Irina Velsko, St John Crean, Lakshmyya Kesavalu
This study explored the origin of age-related granules in the apolipoprotein E gene knockout (ApoE(-/-)) B6 background mice brains following chronic gingival infection with Porphyromonas gingivalis for 24 weeks. Intracerebral localization of P. gingivalis was detected by fluorescence in situ hybridization (FISH) and its protease by immunohistochemistry. The age-related granules were observed by periodic acid-Schiff (PAS), silver impregnation, and immunostaining. FISH showed intracerebral dissemination of P...
2017: Journal of Oral Microbiology
https://www.readbyqxmd.com/read/28324647/metabolism-and-distribution-of-clozapine-n-oxide-implications-for-nonhuman-primate-chemogenetics
#12
Jessica Raper, J Scott Daniels, Ryan D Morrison, Leonard Howell, Jocelyne Bachevalier, Thomas Wichmann, Adriana Galvan
The use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in neuroscience has rapidly expanded in rodent studies, but has lagged behind in nonhuman primate (NHP) experiments, slowing the development of this method for therapeutic use in humans. One reason for the slow adoption of DREADD technology in primates is that the pharmacokinetic properties and bioavailability of clozapine-n-oxide (CNO), the most commonly used ligand for human muscarinic (hM) DREADDs, are not fully described in primates...
March 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28323646/endothelial-cells-and-lymphatics-at-the-interface-between-the-immune-and-central-nervous-systems-implications-for-multiple-sclerosis
#13
Céline Meyer, Guillaume Martin-Blondel, Roland S Liblau
PURPOSE OF REVIEW: The central nervous system (CNS) has a unique relationship with the immune system. This review highlights the distinct roles of lymphatic vessels and endothelial cells in the interface between CNS and immune cells and invites to revisit the concept of CNS immune privilege. RECENT FINDINGS: T cells can follow several routes to penetrate the CNS parenchyma but may also benefit, together with antigen-loaded presenting cells, from the newly described lymphatic network to exit the CNS...
March 18, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28323022/astrocyte-heme-oxygenase-1-reduces-mortality-and-improves-outcome-after-collagenase-induced-intracerebral-hemorrhage
#14
Jing Chen-Roetling, Pramod Kamalapathy, Yang Cao, Wei Song, Hyman M Schipper, Raymond F Regan
Pharmacotherapies that increase CNS expression of heme oxygenase-1 (HO-1) and other antioxidant proteins have improved outcome in experimental models of spontaneous intracerebral hemorrhage (ICH). In order to more specifically investigate the relationship between HO-1 and ICH outcome, mice expressing human HO-1 driven by the glial fibrillary acidic protein (GFAP) promoter (GFAP·HMOX1 mice) were tested in a model of in situ parenchymal hemorrhage. Injection of collagenase into the striata of wild-type (WT) mice resulted in a 26...
March 17, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28322979/3-4-methylenedioxymethamphetamine-mdma-ecstasy-produces-edema-due-to-bbb-disruption-induced-by-mmp-9-activation-in-rat-hippocampus
#15
Mercedes Pérez-Hernández, María Encarnación Fernández-Valle, Ana Rubio-Araiz, Rebeca Vidal, María Dolores Gutiérrez-López, Esther O'Shea, María Isabel Colado
The recreational drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier (BBB) integrity in rats through an early P2X7 receptor-mediated event which induces MMP-9 activity. Increased BBB permeability often causes plasma proteins and water to access cerebral tissue leading to vasogenic edema formation. The current study was performed to examine the effect of a single neurotoxic dose of MDMA (12.5 mg/kg, i.p.) on in vivo edema development associated with changes in the expression of the perivascular astrocytic water channel, AQP4, as well as in the expression of the tight-junction (TJ) protein, claudin-5 and Evans Blue dye extravasation in the hippocampus of adult male Dark Agouti rats...
March 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28322975/a-polymeric-micelle-magnetic-resonance-imaging-mri-contrast-agent-reveals-blood-brain-barrier-bbb-permeability-for-macromolecules-in-cerebral-ischemia-reperfusion-injury
#16
Kouichi Shiraishi, Zuojun Wang, Daisuke Kokuryo, Ichio Aoki, Masayuki Yokoyama
Blood-brain barrier (BBB) opening is a key phenomenon for understanding ischemia-reperfusion injuries that are directly linked to hemorrhagic transformation. The recombinant human tissue-type plasminogen activator (rtPA) increases the risk of symptomatic intracranial hemorrhages. Recent imaging technologies have advanced our understanding of pathological BBB disorders; however, an ongoing challenge in the pre-"rtPA treatment" stage is the task of developing a rigorous method for hemorrhage-risk assessments...
March 16, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28321581/neurobehavioural-toxicity-of-iron-oxide-nanoparticles-in-mice
#17
Vasanth Dhakshinamoorthy, Vijayprakash Manickam, Ekambaram Perumal
Iron oxide nanoparticles (Fe2O3-NPs) are widely used in various biomedical applications, extremely in neurotheranostics. Simultaneously, Fe2O3-NP usage is of alarming concern, as its exposure to living systems causes deleterious effects due to its redox potential. However, study on the neurobehavioural impacts of Fe2O3-NPs is very limited. In this regard, adult male mice were intraperitoneally administered with Fe2O3-NPs (25 and 50 mg/kg body weight) once a week for 4 weeks. A significant change in locomotor behaviour and spatial memory was observed in Fe2O3-NP-treated animals...
March 20, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28320656/targeting-effects-on-the-volume-of-the-focused-ultrasound-induced-blood-brain-barrier-opening-in-non-human-primates-in-vivo
#18
Maria Eleni Karakatsani, Gesthimani Samiotaki, Matthew Downs, Vincent Ferrera, Elisa Konofagou
Drug delivery to subcortical regions is susceptible to the blood-brain barrier (BBB) impeding the molecular exchange between the blood stream and the brain parenchyma. Focused ultrasound coupled with the administration of microbubbles has been proven to open the BBB locally, transiently and non-invasively both in rodents and in Non-Human-Primates (NHPs). The development of this disruption technique independent of MRI monitoring is of primordial importance yet restrained to the targeting optimization. The current paper establishes the linear relationship of the incidence angle with the volume of BBB opening (VBBB) and the Peak Negative Pressure (PNP) when sonicating the Caudate Nucleus and the Putamen region of five non-human-primates...
March 13, 2017: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
https://www.readbyqxmd.com/read/28320270/role-of-nerve-growth-factor-in-plasticity-of-forebrain-cholinergic-neurons
#19
REVIEW
N K Isaev, E V Stelmashook, E E Genrikhs
Neuronal plastic rearrangements during the development and functioning of neurons are largely regulated by trophic factors, including nerve growth factor (NGF). NGF is also involved in the pathogenesis of Alzheimer's disease. In the brain, NGF is produced in structures innervated by basal forebrain cholinergic neurons and retrogradely transported along the axons to the bodies of cholinergic neurons. NGF is essential for normal development and functioning of the basal forebrain; it affects formation of the dendritic tree and modulates the activities of choline acetyltransferase and acetylcholinesterase in basal forebrain neurons...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#20
Alberto Azzalin, Giulia Nato, Elena Parmigiani, Francesca Garello, Annalisa Buffo, Lorenzo Magrassi
Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
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