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blood brain barrier permeability

Grishma N Pawar, Neha N Parayath, Angela L Nocera, Benjamin S Bleier, Mansoor M Amiji
Delivering therapeutics across the blood-brain barrier (BBB) for treating central nervous system (CNS) diseases is one of the biggest challenges today as the BBB limits the uptake of molecules greater than 500 Da into the CNS. Here we describe a novel trans-nasal mucosal drug delivery as an alternative to the intranasal drug delivery to overcome its limitations and deliver high molecular weight (HMW) therapeutics efficiently to the brain. This approach is based on human endoscopic skull base surgical techniques in which a surgical defect is repaired by engrafting semipermeable nasal mucosa over a skull base defect...
2018: PloS One
Elaine Hui-Chien Lee, Sherlyn Sheau-Chin Lim, Kah-Hay Yuen, Chong-Yew Lee
OBJECTIVES: This study aims to investigate the blood-brain barrier (BBB) permeability of curcumin analogues with shortened linkers and their ability to protect against amyloid-beta toxicity in a whole organism model. METHOD: Four curcumin analogues were synthesized. These analogues and curcumin were evaluated for their BBB permeability in the parallel artificial membrane permeability assay. The transgenic Caenorhabditis elegansGMC101 that expresses human Aβ1-42 was treated with the compounds to evaluate their ability to delay Aβ-induced paralysis...
December 4, 2018: Journal of Pharmacy and Pharmacology
Belma Zengin Kurt
In the present study, 14 novel naphthyridine-11-amine derivatives were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. 12-(4-Fluorophenyl)-1,2,3,4,7,8,9,10-octahydrodibenzo[b,g][1, 8]naphthyridin-11-amine (4a) was found to be the most potent AChE inhibitor with IC50 value of 0.091 µM, and 12-(2,3-dimethoxyphenyl)-1,2,3,4,7,8,9,10-octahydrodibenzo[b,g][1,8]naphthyridin-11-amine (4h) exhibited the strongest inhibition against BuChE with IC50 value of 0...
December 4, 2018: Molecular Diversity
Xuyan Jin, Tae-Ryong Riew, Hong Lim Kim, Soojin Kim, Mun-Yong Lee
Glucose-regulated protein (GRP78) or BiP, a 78-kDa chaperone protein located in the endoplasmic reticulum (ER), has recently been reported to be involved in the neuroglial response to ischemia-induced ER stress. The present study was designed to study the expression patterns of this protein and the cell types involved in the induction of GRP78 expression in rats treated with the mitochondrial toxin 3-nitropropionic acid (3-NP). GRP78 immunoreactivity was almost exclusively localized to striatal neurons in saline-treated controls, but GRP78 expression was induced in activated glial cells, including reactive astrocytes and activated microglia/macrophages, in the striata of rats treated with 3-NP...
2018: Frontiers in Cellular Neuroscience
Jackson G DeStefano, John J Jamieson, Raleigh M Linville, Peter C Searson
The blood-brain barrier (BBB) plays a key role in regulating transport into and out of the brain. With increasing interest in the role of the BBB in health and disease, there have been significant advances in the development of in vitro models. The value of these models to the research community is critically dependent on recapitulating characteristics of the BBB in humans or animal models. However, benchmarking in vitro models is surprisingly difficult since much of our knowledge of the structure and function of the BBB comes from in vitro studies...
December 4, 2018: Fluids and Barriers of the CNS
Ivan Presta, Marco Vismara, Fabiana Novellino, Annalidia Donato, Paolo Zaffino, Elisabetta Scali, Krizia Caterina Pirrone, Maria Francesca Spadea, Natalia Malara, Giuseppe Donato
Recent studies have clarified many still unknown aspects related to innate immunity and the blood-brain barrier relationship. They have also confirmed the close links between effector immune system cells, such as granulocytes, macrophages, microglia, natural killer cells and mast cells, and barrier functionality. The latter, in turn, is able to influence not only the entry of the cells of the immune system into the nervous tissue, but also their own activation. Interestingly, these two components and their interactions play a role of great importance not only in infectious diseases, but in almost all the pathologies of the central nervous system...
December 3, 2018: International Journal of Molecular Sciences
Xiujuan Mi, Li Ran, Lixue Chen, Guangcheng Qin
BACKGROUND: The blood-brain barrier (BBB) is an important anatomical structure of the central nervous system (CNS) that limits the penetration of a variety of substances from the blood into the parenchyma. Dysfunction of the BBB is involved in various CNS disorders, including stroke, inflammation, and pain. However, the evidence concerning its role in migraine is insufficient. OBJECTIVE: This study will investigate whether recurrent headache increases BBB permeability and vascular endothelial growth factor (VEGF) expression in a rat model...
November 2018: Pain Physician
Ryan M Jones, Kullervo Hynynen
Transcranial focused ultrasound (FUS) combined with intravenously circulating microbubbles can transiently and selectively increase blood-brain barrier permeability to enable targeted drug delivery to the central nervous system, and is a technique that has the potential to revolutionize the way neurological diseases are managed in medical practice. Clinical testing of this approach is currently underway in patients with brain tumors, early Alzheimer's disease, and amyotrophic lateral sclerosis. A major challenge that needs to be addressed in order for widespread clinical adoption of FUS-mediated blood-brain barrier permeabilization to occur is the development of systems and methods for real-time treatment monitoring and control, to ensure that safe and effective acoustic exposure levels are maintained throughout the procedures...
December 3, 2018: British Journal of Radiology
Mami Noda, Masataka Ifuku, Md Shamim Hossain, Toshihiko Katafuchi
Fatigue is commonly reported in a variety of illnesses and has major impact on quality of life. Chronic fatigue syndrome (CFS) is a debilitating syndrome of unknown etiology. The clinical symptoms include problems in neuroendocrine, autonomic, and immune systems. It is becoming clear that the brain is the central regulator of CFS. For example, neuroinflammation, especially induced by activation of microglia and astrocytes, may play a prominent role in the development of CFS, though little is known about molecular mechanisms...
2018: Frontiers in Psychiatry
Nikola Sladojevic, Svetlana M Stamatovic, Allison M Johnson, Jennifer Choi, Anna Hu, Sophie Dithmer, Ingolf E Blasig, Richard F Keep, Anuska V Andjelkovic
Recent evidence suggests that blood brain barrier (BBB) recovery and reestablishment of BBB impermeability after stroke is incomplete. This could influence stroke recovery, increase the risk of repeat stroke and be a solid substrate for developing vascular dementia. While accumulating evidence has defined morphological alterations and underlying mechanisms of tight junction (TJ) changes during BBB breakdown in acute stroke, very little is known about the type of alterations and mechanisms in BBB "leakage" found sub-acutely or chronically...
November 30, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Derek Sunil Nowrangi, Devin McBride, Anatol Manaenko, Brandon Dixon, Jiping Tang, John H Zhang
Disruption of the blood-brain barrier results in the formation of edema and contributes to the loss of neurological function following intracerebral hemorrhage (ICH). This study examined insulin-like growth factor-1 (IGF-1) as a treatment and its mechanism of action for protecting the blood-brain barrier after ICH in mice. 171 Male CD-1 mice were subjected to ICH via collagenase or autologous blood. A dose study for recombinant human IGF-1 (rhIGF-1) was performed. Brain water content and behavioral deficits were evaluated at 24 and 72 h after the surgery, and Evans blue extravasation and hemoglobin assay were conducted at 24 h...
November 29, 2018: Experimental Neurology
Teresa Żołek, Orsolya Dömötör, Kinga Ostrowska, Éva A Enyedy, Dorota Maciejewska
The delivery of drugs to the brain is complicated by the multiple factors including low blood-brain barrier (BBB) passive permeability, active BBB efflux systems, and plasma protein binding. Thus, a detailed understanding of the transport of the new potent substances through the membranes is vitally important and their physico-chemical characteristics should be analyzed at first. This work presents an evaluation of drug likeness of eight 7-O-arylpiperazinylcoumarin derivatives with high affinity towards serotoninergic receptors 5-HT1A and 5-HT2A with particular analysis of the requirements for the CNS chemotherapeutics...
November 22, 2018: Bioorganic Chemistry
Cesar D Solís, Teresa Morales
Diminished sensitivity to kainic acid (KA) lesioning action is present in the hippocampus of the lactating dam. Given that KA can alter blood-brain barrier (BBB) permeability, we investigated whether lactation would protect BBB permeability after treatment with this neurotoxin. Adult virgin or lactating (13-15 days pp) female Wistar rats were injected with an i.p. (10 mg/kg b.w.) or i.c.v. (100 ng/1 μl) KA dose. Control groups received a similar volume of vehicle. BBB permeability was assessed by an injection of fluorescent FITC-conjugated dextran tracer (40 kDa, 50 mg/500 μl) or of 4% Evans blue dye (500 μl), given 24 h after KA administration...
November 28, 2018: Brain Research Bulletin
Iqbal Sayeed, Nefize Turan, Donald G Stein, Bushra Wali
Because vitamin D hormone deficiency (VDHdef ) can worsen severity and outcome for ischemic stroke, we examined the role of VDH in maintaining blood-brain-barrier (BBB integrity) in a rat model of stroke. In most types of stroke, the BBB is markedly compromised, potentially leading to a cascade of injury processes and functional deficits, so we examined a number of biomarkers associated with BBB disruption to determine whether VDH deficiency would further compromise the BBB following a stroke. Male Wistar rats were randomly assigned to one of two diet cohorts, VDH-sufficient (VDHsuf ) and VDHdef ...
November 28, 2018: Experimental Neurology
Ranran Zhao, Jie Jiang, Huiwen Li, Min Chen, Renfa Liu, Sujuan Sun, De Ma, Xiaolong Liang, Shumin Wang
BACKGROUND AND PURPOSE: Inflammatory reaction plays a crucial role in cerebral ischemia reperfusion (IR) injury. It has been shown that activated microglia long-term existed in cerebral ischemia and induced second injury. Therefore, we hypothesize that prepared phosphatidylserine (PS)-modified microbubbles (PS-MBs) combined with ultrasound-targeted microbubble destruction (UTMD) can safely open the blood-brain barrier (BBB) and target activated microglia for inflammatory area in the later stage of ischemia reperfusion...
November 30, 2018: Journal of Neuroinflammation
Dan Xu, Songqiang Huang, Hui Wang, Wen Xie
Nuclear receptors (NRs) belong to a family of ligand dependent transcription factors. The target genes of NRs include many drug metabolizing enzymes and transporters. The central nervous system (CNS) bears the expression of NRs, drug metabolizing enzymes and transporters. NRs that express in the brain can be divided into three groups according to their characteristics of ligand binding: steroid hormone receptors, non-steroid hormone receptors, and orphan receptors. The NR-mediated regulation of drug metabolizing enzymes and transporters plays important roles in the metabolism and disposition of drugs in the CNS and the penetration of endogenous and exogenous substances through the blood-brain barrier (BBB)...
December 2, 2018: Drug Metabolism Reviews
William Crowe, Lulu Wang, Zhongwei Zhang, Jasmina Varagic, J Daniel Bourland, Michael D Chan, Amyn A Habib, Dawen Zhao
PURPOSE: To assess early changes in brain metastasis in response to whole brain radiotherapy (WBRT) by longitudinal Magnetic Resonance Imaging (MRI). MATERIALS AND METHODS: Using a 7T system, MRI examination of brain metastases in a breast cancer MDA-MD231-Br mouse model were conducted before and 24 hours after 3 daily fractionations of 4 Gy WBRT. Besides anatomic MRI, diffusion-weighted (DW) MRI and dynamic contrast enhanced (DCE) MRI were applied to study cytotoxic effect and blood-tumor-barrier (BTB) permeability change, respectively...
November 30, 2018: International Journal of Radiation Biology
Yuanyuan You, Ni Wang, Lizhen He, Changzheng Shi, Dong Zhang, Yiyong Liu, Liangping Luo, Tianfeng Chen
Herein we designed and synthesized a cell penetrating peptide- and cancer-targeted molecule-functionalized multi-walled carbon nanotube for precise orthotopic glioma therapy. In addition to reduced toxicity, this nanosystem exhibited enhanced cancer recognition, blood-brain barrier (BBB) penetration, and anticancer activity through increased ROS production.
November 30, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Maarja Andaloussi Mäe, Tian Li, Giacomo Bertuzzi, Elisabeth Raschperger, Michael Vanlandewijck, Liqun He, Khayrun Nahar, Annika Dalheim, Jennifer J Hofmann, Bàrbara Laviña, Annika Keller, Christer Betsholtz, Guillem Genové
Diabetes mellitus is associated with cognitive impairment and various central nervous system pathologies such as stroke, vascular dementia, or Alzheimer's disease. The exact pathophysiology of these conditions is poorly understood. Recent reports suggest that hyperglycemia causes cerebral microcirculation pathology and blood-brain barrier (BBB) dysfunction and leakage. The majority of these reports, however, are based on methods including in vitro BBB modeling or streptozotocin-induced diabetes in rodents, opening questions regarding the translation of the in vitro findings to the in vivo situation, and possible direct effects of streptozotocin on the brain vasculature...
November 29, 2018: Scientific Reports
Annika Keller, Mario Nuvolone, Irina Abakumova, Andra Chincisan, Regina Reimann, Merve Avar, Daniel Heinzer, Simone Hornemann, Josephin Wagner, Daniel Kirschenbaum, Fabian F Voigt, Caihong Zhu, Luca Regli, Fritjof Helmchen, Adriano Aguzzi
Transmissible spongiform encephalopathies (TSEs) are caused by the prion, which consists essentially of PrPSc, an aggregated, conformationally modified form of the cellular prion protein (PrPC). Although TSEs can be experimentally transmitted by intracerebral inoculation, most instances of infection in the field occur through extracerebral routes. The epidemics of kuru and variant Creutzfeldt-Jakob disease were caused by dietary exposure to prions, and parenteral administration of prion-contaminated hormones has caused hundreds of iatrogenic TSEs...
November 2018: PLoS Pathogens
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