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blood brain barrier permeability

Piotr Poznanski, Anna Lesniak, Michal Korostynski, Mariusz Sacharczuk
Several preclinical and clinical studies that deal with the neuropathological consequences of mild traumatic brain injury (mTBI) have focused on unraveling its effect on ethanol drinking behavior. Previous reports describe changes in ethanol consumption, both in animal models of mTBI as well as in patients, after concussive brain injury. However, the neurobiological mechanisms underlying this phenomenon are still poorly understood. In the present study, we used a unique model of mouse lines divergently selected for high (HA) or low (LA) swim stress-induced analgesia to examine the effect of mTBI on ethanol drinking behavior...
October 18, 2018: Addiction Biology
Qun Zheng, Zi-Xian Chen, Meng-Bei Xu, Xiao-Li Zhou, Yue-Yue Huang, Guo-Qing Zheng, Yan Wang
To achieve sufficient blood-brain barrier (BBB), penetration is one of the biggest challenges in the development of diagnostic and therapeutic for central nervous system (CNS) disorders. Here, we conducted a systematic review and meta-analysis to assess the preclinical evidence and possible mechanisms of borneol for improving co-administration of CNS drug delivery in animal models. The electronic literature search was conducted in six databases. Fifty-eight studies with 63 comparisons involved 1137 animals were included...
November 2018: Drug Delivery
Leon M T Dicks, Leané Dreyer, Carine Smith, Anton D van Staden
The intestinal barrier, consisting of the vascular endothelium, epithelial cell lining, and mucus layer, covers a surface of about 400 m2 . The integrity of the gut wall is sustained by transcellular proteins forming tight junctions between the epithelial cells. Protected by three layers of mucin, the gut wall forms a non-permeable barrier, keeping digestive enzymes and microorganisms within the luminal space, separate from the blood stream. Microorganisms colonizing the gut may produce bacteriocins in an attempt to outcompete pathogens...
2018: Frontiers in Microbiology
Kelly R Jacobs, David B Lovejoy
Chronic induction of the kynurenine pathway (KP) contributes to neuroinflammation by producing the excitotoxin quinolinic acid (QUIN). This has led to significant interest in the development of inhibitors of this pathway, particularly in the context of neurodegenerative disease. However, acute spinal cord injury (SCI) also results in deleterious increases in QUIN, as secondary inflammatory processes mediated largely by infiltrating macrophages, become predominant. QUIN mediates significant neurotoxicity primarily by excitotoxic stimulation of the N-methyl-D-aspartate receptor, but other mechanisms of QUIN toxicity are known...
December 2018: Neural Regeneration Research
Chao Zhang, Wei Feng, Elena Vodovozova, Daria Tretiakova, Ivan Boldyrevd, Yusha Li, Jurgen Kürths, Tingting Yu, Oxana Semyachkina-Glushkovskaya, Dan Zhu
The photodynamic (PD) effect has been reported to be efficient for the opening of the blood-brain barrier (BBB), which provides a new informative platform for developing perspective strategies towards brain disease therapy and drug delivery. However, this method is usually performed via craniotomy due to high scattering of the turbid skull. In this work, we employed a newly-developed optical clearing skull window for investigating non-invasive PD-induced BBB opening to high weight molecules and 100-nm fluid-phase liposomes containing ganglioside GM1...
October 1, 2018: Biomedical Optics Express
Xiaofeng Chen, Xiaofei He, Shijian Luo, Yukun Feng, Fengyin Liang, Taotao Shi, Ruxun Huang, Zhong Pei, Zhendong Li
Cerebral cortical microinfarct (CMI) is common in patients with dementia and cognitive decline. Emerging studies reported that intestinal dysfunction influenced the outcome of ischemic stroke and that vagus nerve stimulation (VNS) protected against ischemic stroke. However, the effects of intestinal dysfunction and VNS on CMI are not clear. Therefore, we examined the influence of colitis and VNS on CMI and the mechanisms of VNS attenuating CMI in mice with colitis. CMI was induced using a two-photon laser. Colitis was induced using oral dextran sodium sulfate (DSS)...
2018: Frontiers in Neurology
Bingmei M Fu
The blood-brain barrier (BBB) is a dynamic barrier essential for maintaining the microenvironment of the brain. Although the special anatomical features of the BBB determine its protective role for the central nervous system (CNS) from blood-borne neurotoxins, however, the BBB extremely limits the therapeutic efficacy of drugs into the CNS, which greatly hinders the treatment of major brain diseases. This chapter summarized the unique structures of the BBB; described a variety of in vivo and in vitro experimental methods for determining the transport properties of the BBB and the permeability of the BBB to water, ions, and solutes including nutrients, therapeutic agents, and drug carriers; and presented recently developed mathematical models which quantitatively correlate the anatomical structures of the BBB with its barrier functions...
2018: Advances in Experimental Medicine and Biology
Linping Wang
Aluminum, as a known neurotoxicant, contributes to cognitive dysfunction and may contribute to Alzheimer's disease. The important reason is that aluminum can enter and be deposited in the brain. There have been three routes by which aluminum could enter the brain from systemic circulation or the site of absorption. Aluminum fluxes into brain across the blood-brain barrier (BBB), the choroid plexuses and the nasal cavity. Some factors, such as the increasing of the blood-brain barrier permeability, citric acid and parathyroid hormone (PTH), and vitamin D, can promote aluminum to enter the brain...
2018: Advances in Experimental Medicine and Biology
Wojciech G Lesniak, Chengyan Chu, Anna Jablonska, Yong Du, Martin G Pomper, Piotr Walczak, Miroslaw Janowski
Glioblastoma multiforme (GBM) is the most aggressive and common type of brain cancer. Five-year survival rates are below 12%, even with the most aggressive tri-modal therapies. Poor blood-brain barrier (BBB) permeability of therapeutics is a major obstacle limiting efficacy. Intravenous (IV) administration of bevacizumab (BV) is the standard treatment for GBM. It has been recently demonstrated that single intra-arterial (IA) infusion of BV provides superior therapeutic outcomes in patients with recurrent GBM...
October 12, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Slava Berger, Huy Pho, Thomaz Fleury-Curado, Shannon Bevans-Fonti, Haris Younas, Mi-Kyung Shin, Jonathan C Jun, Frederick Anokye-Danso, Rexford S Ahima, Lynn W Enquist, David Mendelowitz, Alan R Schwartz, Vsevolod Y Polotsky
RATIONALE: Leptin treats upper airway obstruction and alveolar hypoventilation in leptin deficient ob/ob mice. However, obese humans and mice with diet-induced obesity are resistant to leptin due to poor permeability of the blood-brain barrier. We propose that intranasal leptin will bypass leptin resistance and treat sleep disordered breathing in obesity. OBJECTIVES: To assess if intranasal leptin can treat obesity hypoventilation and upper airway obstruction during sleep in mice with diet-induced obesity...
October 12, 2018: American Journal of Respiratory and Critical Care Medicine
Caterina Brighi, Simon Puttick, Stephen Rose, Andrew K Whittaker
Despite significant improvements in the clinical management of glioblastoma, poor delivery of systemic therapies to the entire population of tumour cells remains one of the biggest challenges in the achievement of more effective treatments. On the one hand, the abnormal and dysfunctional tumour vascular network largely limits blood perfusion, resulting in an inhomogeneous delivery of drugs to the tumour. On the other hand, the presence of an intact blood-brain barrier (BBB) in certain regions of the tumour prevents chemotherapeutic drugs from permeating through the tumour vessels and reaching the diseased cells...
October 8, 2018: Advanced Drug Delivery Reviews
Pingyuan Wang, Jia Zhou
Great success has been achieved in small molecule drug discovery programs, making extraordinary contributions for human health, especially in targeted therapy. Taking anticancer drug discovery as an example, small molecules traditionally inhibit the target protein enzyme activities and induce cancer cell apoptosis through the target binding. However, the target protein within tumor cells often recovers its activities, leading to acquired drug-resistance through the overexpression of the target protein or the generation of new mutations in the target protein [1]...
October 9, 2018: Current Topics in Medicinal Chemistry
Jack J Miller, James T Grist, Sébastien Serres, James R Larkin, Angus Z Lau, Kevin Ray, Katherine R Fisher, Esben Hansen, Rasmus Stilling Tougaard, Per Mose Nielsen, Jakob Lindhardt, Christoffer Laustsen, Ferdia A Gallagher, Damian J Tyler, Nicola Sibson
Hyperpolarised MRI with Dynamic Nuclear Polarisation overcomes the fundamental thermodynamic limitations of conventional magnetic resonance, and is translating to human studies with several early-phase clinical trials in progress including early reports that demonstrate the utility of the technique to observe lactate production in human brain cancer patients. Owing to the fundamental coupling of metabolism and tissue function, metabolic neuroimaging with hyperpolarised [1-13 C]pyruvate has the potential to be revolutionary in numerous neurological disorders (e...
October 10, 2018: Scientific Reports
Xue Leng, Jun Ma, Yunhui Liu, Shuyuan Shen, Hai Yu, Jian Zheng, Xiaobai Liu, Libo Liu, Jiajia Chen, Lini Zhao, Xuelei Ruan, Yixue Xue
BACKGROUND: The blood-brain barrier (BBB) strongly restricts the entry of anti-glioma drugs into tumor tissues and thus decreases chemotherapy efficacy. Malignant gliomas are highly invasive tumours that use the perivascular space for invasion and co-opt existing vessels as satellite tumor form. Because regulation of the effect of noncoding RNA on BBB function is attracting growing attention, we investigated the effects of noncoding RNA on the permeability of glioma conditioned normal BBB and the mechanism involved using PIWI-associated RNA piR-DQ590027 as a starting point...
October 11, 2018: Journal of Experimental & Clinical Cancer Research: CR
Kristen M Ahlschwede, Geoffry L Curran, Jens T Rosenberg, Samuel C Grant, Gobinda Sarkar, Robert B Jenkins, Subramanian Ramakrishnan, Joseph F Poduslo, Karunya K Kandimalla
Accumulation of amyloid beta (Aβ) peptides in the cerebral vasculature, referred to as cerebral amyloid angiopathy (CAA), is widely observed in Alzheimer's disease (AD) brain and was shown to accelerate cognitive decline. There is no effective method for detecting cerebrovascular amyloid (CVA) and treat CAA. The targeted nanoparticles developed in this study effectively migrated from the blood flow to the vascular endothelium as determined by using quartz crystal microbalance with dissipation monitoring (QCM-D) technology...
October 6, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Vadim Osadchiy, Clair R Martin, Emeran A Mayer
BACKGROUND AND AIMS: Based largely on results from preclinical studies, the concept of a brain gut microbiome axis has been established, mediating bidirectional communication between the gut, its microbiome and the nervous system. Limited data obtained in humans suggests that alterations in these interactions may play a role in several brain gut disorders. METHODS: We reviewed the preclinical and clinical literature related to the topic of brain gut microbiome interactions...
October 4, 2018: Clinical Gastroenterology and Hepatology
Yoichiro Shinohara, Ayumu Konno, Keisuke Nitta, Yasunori Matsuzaki, Hiroyuki Yasui, Junya Suwa, Keiju Hiromura, Hirokazu Hirai
Adeno-associated virus (AAV)-PHP.B, a capsid variant of AAV serotype 9, is highly permeable to the blood-brain barrier. A major obstacle to the systemic use of AAV-PHP.B is the generation of neutralizing antibodies (NAbs); however, temporal profiles of NAb production after exposure to AAV-PHP.B, and the influence on later AAV-PHP.B administration, remains unknown. To address these, AAV-PHP.Bs expressing either GFP or mCherry by neuron-specific or astrocyte-specific promoters were intravenously administered to mice at various intervals, and brain expression was examined...
October 5, 2018: Molecular Neurobiology
Andrew Wang, Sarah C Huen, Harding H Luan, Kelly Baker, Henry Rinder, Carmen J Booth, Ruslan Medzhitov
Sickness behaviors are a conserved set of stereotypic responses to inflammatory diseases. We recently demonstrated that interfering with inflammation-induced anorexia led to metabolic changes that had profound effects on survival of acute inflammatory conditions. We found that different inflammatory states needed to be coordinated with corresponding metabolic programs to actuate tissue-protective mechanisms. Survival of viral inflammation required intact glucose utilization pathways, whereas survival of bacterial inflammation required alternative fuel substrates and ketogenic programs...
October 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Kelsey E Murphy, Killian Llewellyn, Samuel Wakser, Josef Pontasch, Natasha Samanich, Matthew Flemer, Kenneth Hensley, Dong-Shik Kim, Joshua J Park
Oxidative stress triggers and exacerbates neurodegeneration in Alzheimer's disease (AD). Various antioxidants reduce oxidative stress, but these agents have little efficacy due to poor blood-brain barrier (BBB) permeability. Additionally, single-modal antioxidants are easily overwhelmed by global oxidative stress. Activating nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) and its downstream antioxidant system are considered very effective for reducing global oxidative stress. Thus far, only a few BBB-permeable agents activate the Nrf2-dependent antioxidant system...
October 3, 2018: Journal of Biological Chemistry
M B Lauvsnes, A B Tjensvoll, S S Maroni, I Kvivik, T Grimstad, O J Greve, E Harboe, L G Gøransson, C Putterman, R Omdal
Objective A prevailing hypothesis for neuropsychiatric involvement in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome is that brain reactive autoantibodies enter the brain through a disrupted blood-brain barrier. Our aim was to investigate whether TNF-like weak inducer of apoptosis (TWEAK) plays a role in cerebral involvement in human SLE and primary Sjögren's syndrome, and whether an impaired blood-brain barrier is a prerequisite for neuropsychiatric manifestations. Methods TWEAK was measured in the cerebrospinal fluid and serum and compared with markers of blood-brain barrier permeability (Q-albumin and MRI contrast-enhanced lesions) and S100B, an astrocyte activation marker in 50 SLE and 52 primary Sjögren's syndrome patients...
October 3, 2018: Lupus
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