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Blood-brain barrier

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https://www.readbyqxmd.com/read/27925398/cell-based-biohybrid-drug-delivery-systems-the-best-of-the-synthetic-and-natural-worlds
#1
Samagya Banskota, Parisa Yousefpour, Ashutosh Chilkoti
The goal of drug delivery is to deliver therapeutics to the site of disease while reducing unwanted side effects. In recent years, a diverse variety of synthetic nano and microparticles have been developed as drug delivery systems. The success of these systems for drug delivery lies in their ability to overcome biological barriers such as the blood-brain barrier, to evade immune clearance and avoid nonspecific biodistribution. This Review provides an overview of recent advances in the design of biohybrid drug delivery systems, which combine cells with synthetic systems to overcome some of these biological hurdles...
December 7, 2016: Macromolecular Bioscience
https://www.readbyqxmd.com/read/27925201/vascular-inter-regulation-of-inflammation-molecular-and-cellular-targets-for-cns-therapy
#2
REVIEW
Marta Machado-Pereira, Tiago Santos, Liliana Bernardino, Raquel Ferreira
Angiogenesis and inflammation are clearly interconnected and interdependent processes that are dysregulated in a series of systemic and brain pathologies. Herein, key aspects regarding endothelial cell function and tissue remodelling that are particularly affected or aggravated by inflammation are presented. Most importantly, the cellular and molecular mechanisms involved in the vascular regulation of the inflammatory processes occurring in several brain disorders and how they impact on disease/injury progression are detailed, highlighting potential targets for therapy...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27924726/neurodegenerative-disease-a-perspective-on-cell-based-therapy-in-the-new-era-of-cell-free-nano-therapy
#3
Su M Metcalfe, Sean Bickerton, Tarek Fahmy
Neurodegenerative diseases (NDD) result in irreversible loss of neurons. Dementia develops when disease-induced neuronal loss becomes sufficient to impair both memory and cognitive functioning and, globally, dementia is increasing to epidemic proportions as populations age. In the current era of regenerative medicine intense activity is asking, can loss of endogenous neurons be compensated by replacement with exogenously derived cells that have either direct, or indirect, neurogenic capacity? But, more recently, excitement is growing around an emerging alternative to the cell-based approach - here nanotechnology for targeted delivery of growth factor aims to support and expand resident central nervous system (CNS) stem cells for endogenous repair...
December 6, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27924525/a-three-day-consecutive-fingolimod-administration-improves-neurological-functions-and-modulates-multiple-immune-responses-of-cci-mice
#4
Chuang Gao, Yu Qian, Jinhao Huang, Dong Wang, Wanqiang Su, Peng Wang, Linyue Guo, Wei Quan, Shuo An, Jianning Zhang, Rongcai Jiang
Excessive inflammation after traumatic brain injury (TBI) is a major cause of secondary TBI. Though several inflammatory biomarkers have been postulated as the risk factors of TBI, there has not been any comprehensive description of them. Fingolimod, a new kind of immunomodulatory agent which can diminish various kinds of inflammatory responses, has shown additional therapeutic effects in the treatment of intracranial cerebral hematoma (ICH), ischemia, spinal cord injury (SCI), and many other CNS disorders...
December 6, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27924154/early-diagnosis-of-brain-metastases-using-a-biofluids-metabolomics-approach-in-mice
#5
James R Larkin, Alex M Dickens, Timothy D W Claridge, Claire Bristow, Kleopatra Andreou, Daniel C Anthony, Nicola R Sibson
Over 20% of cancer patients will develop brain metastases. Prognosis is currently extremely poor, largely owing to late-stage diagnosis. We hypothesized that biofluid metabolomics could detect tumours at the micrometastatic stage, prior to the current clinical gold-standard of blood-brain barrier breakdown. Metastatic mammary carcinoma cells (4T1-GFP) were injected into BALB/c mice via intracerebral, intracardiac or intravenous routes to induce differing cerebral and systemic tumour burdens. B16F10 melanoma and MDA231BR-GFP human breast carcinoma cells were used for additional modelling...
2016: Theranostics
https://www.readbyqxmd.com/read/27923718/using-the-cerebrospinal-fluid-to-understand-ingestive-behavior
#6
REVIEW
Stephen C Woods, Aaron A May, Min Liu, Patrick Tso, Denovan P Begg
The cerebrospinal fluid (CSF) offers a window into the workings of the brain and blood-brain barrier (BBB). Molecules that enter into the central nervous system (CNS) by passive diffusion or receptor-mediated transport through the choroid plexus often appear in the CSF prior to acting within the brain. Other molecules enter the CNS by passing through the BBB into the brain's interstitial fluid prior to appearing in the CSF. This pattern is also often observed for molecules synthesized by neurons or glia within the CNS...
December 3, 2016: Physiology & Behavior
https://www.readbyqxmd.com/read/27921254/the-impact-of-vitamin-d-supplementation-on-neurodegeneration-tnf-%C3%AE-concentration-in-hypothalamus-and-csf-to-plasma-ratio-of-insulin-in-high-fat-diet-induced-obese-rats
#7
Ghazaleh Nameni, Ghazaleh Hajiluian, Parviz Shahabi, Mahdieh Abbasalizad Farhangi, Mehran Mesgari-Abbasi, Mohammad-Reza Hemmati, Seyed Mahdi Vatandoust
There is growing evidence that obesity can lead to neurodegeneration induced by pro-inflammatory cytokines such as tumor necrosis factor (TNF-α). Moreover, obesity is associated with reduced transport of insulin through the blood-brain barrier (BBB). Insulin deficiency in the brain especially in the hypothalamus region has neurodegenerative and obesity-promoting effects. Because of the anti-inflammatory and neuroprotective effects of vitamin D, in the current experimental study, we aimed to investigate the effects of vitamin D supplementation on neurodegeneration, TNF-α concentration in the hypothalamus, and cerebrospinal fluid (CSF) to serum ratio of insulin in high-fat-diet-induced obese rats...
December 6, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27920506/polifeprosan-20-3-85-carmustine-slow-release-wafer-in-malignant-glioma-patient-selection-and-perspectives-on-a-low-burden-therapy
#8
REVIEW
Lawrence Kleinberg
Polifeprosan 20 with carmustine (GLIADEL(®)) polymer implant wafer is a biodegradable compound containing 3.85% carmustine (BCNU, bischloroethylnitrosourea) implanted in the brain at the time of planned tumor surgery, which then slowly degrades to release the BCNU chemotherapy directly into the brain thereby bypassing the blood-brain barrier. Carmustine implant wafers were demonstrated to improve survival in randomized placebo-controlled trials in patients undergoing a near total resection of newly diagnosed or recurrent malignant glioma...
2016: Patient Preference and Adherence
https://www.readbyqxmd.com/read/27920202/the-translational-significance-of-the-neurovascular-unit-a-mini-review
#9
Heather L McConnell, Cymon N Kersch, Randall L Woltjer, Edward A Neuwelt
The mammalian brain is supplied with blood by specialized vasculature that is structurally and functionally distinct from that of the periphery. A defining feature of this vasculature is a physical blood-brain barrier (BBB). The BBB separates blood components from the brain microenvironment, regulating the entry and exit of ions, nutrients, macromolecules, and energy metabolites. Over the last two decades, physiological studies of cerebral blood flow dynamics have demonstrated that substantial intercellular communication occurs between cells of the vasculature and the neurons and glia that abut the vasculature...
December 5, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27919501/soluble-serum-vcam-1-whole-blood-mrna-expression-and-treatment-response-in-natalizumab-treated-multiple-sclerosis
#10
E R Petersen, H B Søndergaard, A B Oturai, Peh Jensen, P S Sorensen, F Sellebjerg, L Börnsen
BACKGROUND: Natalizumab reduces disease activity in multiple sclerosis (MS). Natalizumab binds to the very late antigen-4 and inhibits vascular cell adhesion molecule-1 (VCAM-1)-mediated transmigration of immune cells across the blood-brain-barrier. This is associated with decreased serum concentrations of soluble (s)VCAM-1 and an altered composition of immune cell-subsets in the blood. OBJECTIVE: We aimed to examine if sVCAM-1 serum concentrations and whole blood mRNA expression levels of immune activation biomarkers is associated with disease activity in natalizumab-treated MS-patients...
November 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27919332/effects-of-ionizing-radiation-on-the-mammalian-brain
#11
Daniela Hladik, Soile Tapio
Epidemiological studies on the atomic-bomb survivors, cancer survivors and occupational cohorts provide strong evidence for multifaceted damage to brain after ionizing radiation. Radiation-induced late effects may manifest as brain tumors or cognitive impairment. Decreased neurogenesis and differentiation, alteration in neural structure and synaptic plasticity as well as increased oxidative stress and inflammation are suggested to contribute to adverse effects in the brain. In addition to neural stems cells, several brain-specific mature cell types including endothelial and glial cells are negatively affected by ionizing radiation...
October 2016: Mutation Research
https://www.readbyqxmd.com/read/27918993/tetrahydropyranodiquinolin-8-amines-as-new-non-hepatotoxic-antioxidant-and-acetylcholinesterase-inhibitors-for-alzheimer-s-disease-therapy
#12
Youssef Dgachi, Olga Sokolov, Vincent Luzet, Justyna Godyń, Dawid Panek, Alexandre Bonet, Hélène Martin, Isabel Iriepa, Ignacio Moraleda, Cristina García-Iriepa, Jana Janockova, Lysiane Richert, Ondrej Soukup, Barbara Malawska, Fakher Chabchoub, José Marco-Contelles, Lhassane Ismaili
Herein we report an efficient two step synthesis and biological assessment of 12 racemic tetrahydropyranodiquinolin-8-amines derivatives as antioxidant, cholinesterase inhibitors and non-hepatotoxic agents. Based on the results of the primary screening, we identified 7-(3-methoxyphenyl)-9,10,11,12-tetrahydro-7H-pyrano[2,3-b:5,6-h']diquinolin-8-amine (2h) as a particularly interesting non-hepatotoxic compound that shows moderate antioxidant activity (1.83 equiv Trolox in the ORAC assay), a non competitive inhibition of hAChE (IC50 = 0...
November 23, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27918249/abcb1-genotyping-in-the-treatment-of-depression
#13
Tanja Maria Brückl, Manfred Uhr
P-glycoprotein (P-gp), the gene product of ABCB1, is a drug transporter at the blood-brain barrier and could be a limiting factor for entrance of antidepressants into the brain, the target site of antidepressant action. Animal studies showed that brain concentrations of many antidepressants depend on P-gp. In humans, ABCB1 genotyping in the treatment of depression rests on the assumption that genetic variations in ABCB1 explain individual differences in antidepressant response via their effects on P-gp expression at the blood-brain barrier...
December 5, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27917302/characterization-of-the-blood-brain-barrier-in-pediatric-central-nervous-system-neoplasms
#14
Christopher S Hong, Winson Ho, Martin G Piazza, Abhik Ray-Chaudhury, Zhengping Zhuang, John D Heiss
OBJECTIVE: The normal blood-brain barrier (BBB) is composed of tight junctions between endothelial cells and surrounding astrocyte foot processes. Breakdown of the physiological astrocyte-endothelial cell relationship occurs in adult metastatic and primary brain tumors. However, the astrocyte-endothelial cell relationship has not been studied in pediatric tumors. MATERIALS AND METHODS: Utilizing specimens from cases of pilocytic astrocytoma (n = 5), medulloblastoma (n = 5), and low-grade diffuse astrocytoma (n = 1), immunofluorescence were performed using primary antibodies against CD31, glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQ4)...
2016: Journal of Interdisciplinary Histopathology
https://www.readbyqxmd.com/read/27917173/live-imaging-of-immune-responses-in-experimental-models-of-multiple-sclerosis
#15
REVIEW
Barbara Rossi, Gabriela Constantin
Experimental autoimmune encephalomyelitis (EAE) is the most common animal model of multiple sclerosis (MS), a chronic inflammatory autoimmune disease of the central nervous system (CNS) characterized by multifocal perivascular infiltrates that predominantly comprise lymphocytes and macrophages. During EAE, autoreactive T cells first become active in the secondary lymphoid organs upon contact with antigen-presenting cells (APCs), and then gain access to CNS parenchyma, through a compromised blood-brain barrier, subsequently inducing inflammation and demyelination...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27916828/enhancing-anticancer-effect-of-gefitinib-across-the-blood-brain-barrier-model-using-liposomes-modified-with-one-%C3%AE-helical-cell-penetrating-peptide-or-glutathione-and-tween-80
#16
Kuan-Hung Lin, Shu-Ting Hong, Hsiang-Tsui Wang, Yu-Li Lo, Anya Maan-Yuh Lin, James Chih-Hsin Yang
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib, have been demonstrated to effectively treat the patients of extracranial non-small cell lung cancer (NSCLC). However, these patients often develop brain metastasis (BM) during their disease course. The major obstacle to treat BM is the limited penetration of anticancer drugs across the blood-brain barrier (BBB). In the present study, we utilized gefitinib-loaded liposomes with different modifications to improve gefitinib delivery across the in vitro BBB model of bEnd...
November 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916702/chronic-kidney-disease-accelerates-cognitive-impairment-in-a-mouse-model-of-alzheimer-s-disease-through-angiotensin-ii
#17
Takashi Nakagawa, Yu Hasegawa, Ken Uekawa, Shokei Kim-Mitsuyama
Epidemiological studies suggest that chronic kidney disease (CKD) is a significant risk factor in the development of cognitive decline. However, the exact role of CKD in cognitive impairment or dementia is unclear. This work was performed to examine the potential impact of CKD on cognitive impairment in Alzheimer's disease (AD), focusing on angiotensin II. (1) CKD was induced in 5XFAD mice, an AD model mouse, and wild-type mice by feeding adenine-containing diet and the effect on cognitive function was compared between both strains...
December 1, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27916657/pharmacokinetic-analysis-and-drug-delivery-efficiency-of-the-focused-ultrasound-induced-blood-brain-barrier-opening-in-non-human-primates
#18
Gesthimani Samiotaki, Maria Eleni Karakatsani, Amanda Buch, Stephanos Papadopoulos, Shih Ying Wu, Sachin Jambawalikar, Elisa E Konofagou
PURPOSE: Focused Ultrasound (FUS) in conjunction with systemically administered microbubbles has been shown to open the Blood-Brain Barrier (BBB) locally, non-invasively and reversibly in rodents and non-human primates (NHP), suggesting the immense potential of this technique. The objective of this study entailed the investigation of the physiologic changes in the brain following the FUS-induced BBB opening and their relationship with the underlying anatomy. MATERIALS AND METHODS: Pharmacokinetic analysis was implemented in NHP's that received FUS at various acoustic pressures...
December 1, 2016: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/27916423/effect-of-ulinastatin-on-the-permeability-of-the-blood-brain-barrier-on-rats-with-global-cerebral-ischemia-reperfusion-injury-as-assessed-by-mri
#19
Ming Liu, Jie Shen, Fan Zou, Yunfeng Zhao, Bing Li, Mingxia Fan
The study was designed to evaluate the effect of ulinastatin on the permeability of the blood-brain barrier in rats with global cerebral ischemia/reperfusion injury using MRI. A total of 108 Wistar rats (240 g-280g) were randomly divided into three groups (n=36): sham group (S group), global cerebral ischemia/reperfusion model group (GCI/R group) and 10,000U/kg ulinastatin intervention group (U group). Fifty-four Wistar rats were used for MRI, and the rest were used for Evans Blue(EB)analysis. We used the Pulsinelli four-vessel occlusion (4-VO) model of global cerebral ischemia/reperfusion to investigate the integrity of the blood-brain barrier with Evans Blue (EB) staining at 15min after ischemia and at 6h (n=6), 24h (n=6), and 48h (n=6) after reperfusion to assess blood-brain barrier permeability with MRI...
December 1, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27915995/lack-of-p-glycoprotein-results-in-impairment-of-removal-of-beta-amyloid-and-increased-intraparenchymal-cerebral-amyloid-angiopathy-after-active-immunization-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#20
Sascha Brückmann, Anja Brenn, Markus Grube, Katharina Niedrig, Silva Holtfreter, Oliver von Bohlen Und Halbach, Martin Groschup, Markus Keller, Silke Vogelgesang
Immunization against beta-amyloid (Aβ) reduces cerebral Aβ deposits and improves cognitive capacities in transgenic mouse models, and thus has been considered a promising disease-modifying therapeutic approach for Alzheimer's disease (AD). Although clinical trials in AD patients have yielded evidence for clearance of parenchymal Aβ plaques, Aβ increases in blood vessels of treated patients. We hypothesize that an age-related decline in the mechanisms that clear Aβ from the brain might be at least in part responsible for the failure to purge and re-distribute Aβ...
December 1, 2016: Current Alzheimer Research
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