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Blood brain barrier

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https://www.readbyqxmd.com/read/28103265/rabbit-model-of-human-gliomas-implications-for-intra-arterial-drug-delivery
#1
Huamin Qin, Miroslaw Janowski, Monica S Pearl, Izabela Malysz-Cymborska, Shen Li, Charles G Eberhart, Piotr Walczak
The prognosis for malignant brain tumors remains poor despite a combination of surgery, radiotherapy, and chemotherapy. This is partly due to the blood-brain barrier, a major obstacle that prevents therapeutic agents from effectively reaching the tumor. We have recently developed a method for precise and predictable opening of the blood-brain barrier via the intra-arterial administration of mannitol, a hyperosmolar agent, in a rabbit model, whose vascular anatomy facilitates the use of standard interventional neuroradiology techniques and devices...
2017: PloS One
https://www.readbyqxmd.com/read/28101766/crossing-the-blood-brain-barrier-recent-advances-in-drug-delivery-to-the-brain
#2
Mayur M Patel, Bhoomika M Patel
CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting...
January 18, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28099097/blood-brain-barrier-leakage-in-patients-with-early-alzheimer-disease
#3
Harm J van de Haar, Saartje Burgmans, Jacobus F A Jansen, Matthias J P van Osch, Mark A van Buchem, Majon Muller, Paul A M Hofman, Frans R J Verhey, Walter H Backes
No abstract text is available yet for this article.
February 2017: Radiology
https://www.readbyqxmd.com/read/28098992/mechanistic-insights-into-tunable-metal-mediated-hydrolysis-of-amyloid-%C3%AE-peptides
#4
Jeffrey S Derrick, Jiwan Lee, Shin Jung C Lee, Yujeong Kim, Eunju Nam, Hyeonwoo Tak, Juhye Kang, Misun Lee, Sun Hee Kim, Kiyoung Park, Jaeheung Cho, Mi Hee Lim
An amyloidogenic peptide, amyloid-β (Aβ), has been implicated as a contributor to the neurotoxicity of Alzheimer's disease (AD) that continues to present a major socioeconomic burden for our society. Recently, the use of metal complexes capable of cleaving peptides has arisen as an efficient tactic for amyloid management; unfortunately, little has been reported to pursue this strategy. Herein, we report a novel approach to validate the hydrolytic cleavage of divalent metal complexes toward two major isoforms of Aβ (Aβ40 and Aβ42) and tune their proteolytic activity based on the choice of metal centers (M = Co, Ni, Cu, and Zn) which could be correlated to their anti-amyloidogenic properties...
January 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28098771/breast-cancer-brain-metastases-clonal-evolution-in-clinical-context
#5
REVIEW
Jodi M Saunus, Amy E McCart Reed, Zhun Leong Lim, Sunil R Lakhani
Brain metastases are highly-evolved manifestations of breast cancer arising in a unique microenvironment, giving them exceptional adaptability in the face of new extrinsic pressures. The incidence is rising in line with population ageing, and use of newer therapies that stabilise metastatic disease burden with variable efficacy throughout the body. Historically, there has been a widely-held view that brain metastases do not respond to circulating therapeutics because the blood-brain-barrier (BBB) restricts their uptake...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28098709/multimodal-imaging-during-the-evolution-of-blood-brain-barrier-disruption-maculopathy
#6
Bikramjit P Pal, Tapani Palosaari, Tero Kivelä
PURPOSE: To highlight the course of blood-brain barrier disruption maculopathy in a patient with successfully managed relapsed central nervous system lymphoma. METHODS: Case report with fundus autofluorescence and optical coherence tomography imaging, and literature review. RESULTS: A 57-year-old patient diagnosed with central nervous system large B-cell lymphoma had a normal ophthalmic evaluation on his first visit. Subsequently, when his malignancy recurred locally, he was started on blood-brain barrier disruption therapy and intraarterial methotrexate...
January 16, 2017: Retinal Cases & Brief Reports
https://www.readbyqxmd.com/read/28098193/non-pathogenic-tissue-resident-cd8-t-cells-uniquely-accumulate-in-the-brains-of-lupus-prone-mice
#7
Peter A Morawski, Chen-Feng Qi, Silvia Bolland
Severe lupus often includes psychiatric and neurological sequelae, although the cellular contributors to CNS disease remain poorly defined. Using intravascular staining to discriminate tissue-localized from blood-borne cells, we find substantial accumulation of CD8(+) T cells relative to other lymphocytes in brain tissue, which correlates with lupus disease and limited neuropathology. This is in contrast to all other affected organs, where infiltrating CD4(+) cells are predominant. Brain-infiltrating CD8(+) T cells represent an activated subset of those found in the periphery, having a resident-memory phenotype (CD69(+)CD122(-)PD1(+)CD44(+)CD62L(-)) and expressing adhesion molecules (VLA-4(+)LFA-1(+)) complementary to activated brain endothelium...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098158/pericytes-from-mesenchymal-stem-cells-as-a-model-for-the-blood-brain-barrier
#8
Xiaohe Tian, Oliver Brookes, Giuseppe Battaglia
Blood brain-barrier (BBB) in vitro models have been widely reported in studies of the BBB phenotype. However, established co-culture systems involve brain endothelial cells, astrocytes, neurons and pericytes, and therefore are often consuming and technically challenging. Here we use mesenchymal system cells (MSC) as a potential substitute for pericytes in a BBB model. Both MSC and pericyte markers in 2D culture environment were evaluated on different extracellular matrix compositions. Further experiments indicated that MSC contributed in a similar manner to pericytes in a co-cultured 3D model on increasing trans-endothelial electric resistance (TEER) and decreasing permeability against macromolecules...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097491/small-interfering-rna-targeting-dickkopf-1-contributes-to-neuroprotection-after-intracerebral-hemorrhage-in-rats
#9
Zhihua Li, Xi Chen, Xiaoyang Zhang, Xiuhua Ren, Xuemei Chen, Jing Cao, Weidong Zang, Xianzhi Liu, Fuyou Guo
Excessive Dickkopf-1 (Dkk-1) plays a vital role in secondary brain injury following ischemic stroke and psychotic disease. However, it is unclear whether an increased expression of Dkk-1 occurred after intracerebral hemorrhage (ICH). The present study examined the potential role of Dkk-1 after ICH. ICH was induced by a single injection of autologous blood into the basal ganglia of rats. Dkk-1 protein levels in brain tissue and serum were detected by enzyme-linked immunosorbent assay after ICH. Rats were treated with small interfering RNA targeting Dkk-1 (siDkk-1) or vehicle following ICH...
January 17, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28095676/radiosynthesis-and-evaluation-of-11-c-3-hydroxycyclopent-1-enecarboxylic-acid-as-potential-pet-ligand-for-the-high-affinity-%C3%AE-hydroxybutyric-acid-binding-sites
#10
Claus H Jensen, Hanne D Hansen, Tina Bay, Stine B Vogensen, Szabolcs Lehel, Louise Thiesen, Christoffer Bundgaard, Rasmus P Clausen, Gitte M Knudsen, Matthias M Herth, Petrine Wellendorph, Bente Frølund
γ-Hydroxybutyric acid (GHB) is an endogenous neuroactive substance and proposed neurotransmitter with affinity for both low- and high-affinity binding sites. A radioligand with high and specific affinity toward the high-affinity GHB binding site would be a unique tool toward a more complete understanding of this population of binding sites. With its high specific affinity and monocarboxylate transporter (MCT1) mediated transport across the blood-brain barrier in pharmacological doses, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) seems like a suitable PET radiotracer candidate...
January 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28094959/noninvasive-targeted-transcranial-neuromodulation-via-focused-ultrasound-gated-drug-release-from-nanoemulsions
#11
Raag D Airan, Randall A Meyer, Nicholas P K Ellens, Kelly Rhodes, Keyvan Farahani, Martin G Pomper, Shilpa D Kadam, Jordan J Green
Targeted, noninvasive neuromodulation of the brain of an otherwise awake subject could revolutionize both basic and clinical neuroscience. Towards this goal, we have developed nanoparticles that allow noninvasive uncaging of a neuromodulatory drug - in this case the small molecule anesthetic propofol - upon the application of focused ultrasound. These nanoparticles are composed of biodegradable and biocompatible constituents and are activated using sonication parameters that are readily achievable by current clinical transcranial focused ultrasound systems...
January 17, 2017: Nano Letters
https://www.readbyqxmd.com/read/28094605/multiple-protocadherins-are-expressed-in-brain-microvascular-endothelial-cells-and-might-play-a-role-in-tight-junction-protein-regulation
#12
Christina Dilling, Norbert Roewer, Carola Y Förster, Malgorzata Burek
Protocadherins (Pcdhs) are a large family of cadherin-related molecules. They play a role in cell adhesion, cellular interactions, and development of the central nervous system. However, their expression and role in endothelial cells has not yet been characterized. Here, we examined the expression of selected clustered Pcdhs in endothelial cells from several vascular beds. We analyzed human and mouse brain microvascular endothelial cell (BMEC) lines and primary cells, mouse myocardial microvascular endothelial cell line, and human umbilical vein endothelial cells...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28094184/in-vivo-evaluation-of-igf1r-ir-pet-ligand-18-f-bms-754807-in-rodents
#13
Jaya Prabhakaran, Stephen L Dewey, Richard McClure, Norman R Simpson, Mohammed N Tantawy, J John Mann, Wellington Pham, J S Dileep Kumar
In vivo evaluation of [(18)F]BMS-754807 binding in mice and rats using microPET and biodistribution methods is described herein. The radioligand shows consistent binding characteristics, in vivo, in both species. Early time frames of the microPET images and time activity curves of brain indicate poor penetration of the tracer across the blood brain barrier (BBB) in both species. However, microPET experiments in mice and rats show high binding of the radioligand outside the brain to heart, pancreas and muscle, the organs known for higher expression of IGF1R/1R...
January 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28093709/molecular-genetic-and-epigenetic-basis-of-multiple-sclerosis
#14
Zohreh Hojati
Multiple Sclerosis (MS) is a chronic immune-mediated disease of spinal cord and brain. The initial event in MS occurs when activated CD4(+) T cells in periphery exacerbates immune responses by stimulating immune cells such as B cells, CD8(+) cells, mast cells, granulocytes and monocytes. These proinflammatory cells pass blood brain barrier by secreting proinflammatory cytokines including TNF-α and INF-γ which activate adhesion factors. APCs (antigen-presenting cells) reactivate CD4(+) T cells after infiltrating the CNS and CD4(+) T cells produce cytokines and chemokines...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28093705/manipulation-of-oxygen-and-endoplasmic-reticulum-stress-factors-as-possible-interventions-for-treatment-of-multiple-sclerosis-evidence-for-and-against
#15
Paul Eggleton, Gary R Smerdon, Janet E Holley, Nicholas J Gutowski
Multiple sclerosis (MS) is normally considered a chronic inflammatory disease of the central nervous system (CNS), where T-cells breaching the blood brain barrier react against proteins of the axonal myelin sheaths, leading to focal plaques and demyelination in the brain and spinal cord. Many current therapies are immunosuppressive in nature and are designed to target the immune system at an early stage of the disease. But there is no cure and MS may evolve into a neurodegenerative disease, where immunomodulatory treatments appear less effective...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28093570/vitamin-d-administration-cognitive-function-bbb-permeability-and-neuro-inflammatory-factors-in-high-fat-diet-induced-obese-rats
#16
G Hajiluian, G Nameni, P Shahabi, M Mesgari-Abbasi, S Sadigh-Eteghad, M A Farhangi
OBJECTIVES: The purpose of this research is to investigate the effects of vitamin D administration on cognitive function, nuclear factor Kappa-B (NF-kB), brain derived neurotrophic factor (BDNF) concentration in the hippocampus and blood-brain barrier (BBB) permeability in high-fat diet (HFD) induced obese rats. METHODS: Male Wistar rats were fed either a control diet or HFD for 16 weeks (n=20); then each group was randomized into two subgroups supplemented orally with 500 IU/kg vitamin D for 5 weeks...
January 17, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28093288/assessing-the-impact-of-lithium-chloride-on-the-expression-of-p-glycoprotein-at-the-blood-brain-barrier
#17
Stephanie A Newman, Yijun Pan, Jennifer L Short, Joseph A Nicolazzo
In addition to extruding drugs from the brain, P-glycoprotein (P-gp) at the blood-brain barrier (BBB) facilitates the brain-to-blood clearance of β-amyloid (Aβ) and is down-regulated in Alzheimer's disease (AD). Studies suggest that the mood-stabilising drug lithium exerts a protective effect against AD. While the mechanisms underlying this effect are not fully understood, evidence suggests that lithium chloride (LiCl) increases P-gp expression in vitro, albeit at concentrations substantially outside the therapeutic window...
January 13, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28093036/combining-nanoscale-magnetic-nimodipine-liposomes-with-magnetic-resonance-image-for-parkinson-s-disease-targeting-therapy
#18
Bingshuo Ji, Meili Wang, Dawei Gao, Shanshan Xing, Lei Li, Lanxiang Liu, Min Zhao, Ximing Qi, Kun Dai
AIM: To enhance drug targeting and blood-brain barrier penetration for Parkinson's disease (PD), a novel nanoscale magnetic nimodipine (NMD) delivery system was designed and prepared. MATERIALS & METHODS: The PD rats were established and treated with free NMD or Fe3O4-modified NMD liposomes (Fe3O4-NMD-lips). Then, factional anisotropy values were measured by MRI to evaluate therapy efficacy. RESULTS: Fe3O4-NMD-lips showed the best neuroprotective effect, and the NMD concentration of lesions was 2...
January 17, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28092695/absorption-distribution-and-excretion-of-the-anti-tuberculosis-drug-delamanid-in-rats-extensive-tissue-distribution-suggests-potential-therapeutic-value-for-extrapulmonary-tuberculosis
#19
Masakazu Shibata, Yoshihiko Shimokawa, Katsunori Sasahara, Noriaki Yoda, Hiroyuki Sasabe, Mitsunari Suzuki, Ken Umehara
Delamanid (OPC-67683, Deltyba(TM) , nitro-dihydro-imidazooxazoles derivative) is approved for the treatment of adult pulmonary multidrug-resistant tuberculosis. The absorption, distribution, and excretion of delamanid-derived radioactivity were investigated after a single oral administration of (14) C-delamanid at 3 mg/kg to rats. In both male and female rats, radioactivity in blood and all tissues reached peak levels by 8 or 24 hours postdose, and thereafter decreased slowly. Radioactivity levels were 3- to 5-fold higher in lung tissue at time to maximum concentration compared with plasma...
January 16, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28092660/the-role-of-peripheral-immune-cells-in-the-cns-in-steady-state-and-disease
#20
REVIEW
Marco Prinz, Josef Priller
The CNS is protected by the immune system, including cells that reside directly within the CNS and help to ensure proper neural function, as well as cells that traffic into the CNS with disease. The CNS-resident immune system is comprised mainly of innate immune cells and operates under homeostatic conditions. These myeloid cells in the CNS parenchyma and at CNS-periphery interfaces are highly specialized but also extremely plastic cells that immediately react to any changes in CNS homeostasis and become reactive in the context of neurodegenerative disorders such as Alzheimer's disease or Parkinson's disease...
January 16, 2017: Nature Neuroscience
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