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blood brain barrier permeability

Mazen M Jamil Al-Obaidi, Mohd Nasir Mohd Desa
This review aims to elucidate the different mechanisms of blood brain barrier (BBB) disruption that may occur due to invasion by different types of bacteria, as well as to show the bacteria-host interactions that assist the bacterial pathogen in invading the brain. For example, platelet-activating factor receptor (PAFR) is responsible for brain invasion during the adhesion of pneumococci to brain endothelial cells, which might lead to brain invasion. Additionally, the major adhesin of the pneumococcal pilus-1, RrgA is able to bind the BBB endothelial receptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1), thus leading to invasion of the brain...
August 16, 2018: Cellular and Molecular Neurobiology
Dan Lu, Yanfang Liu, Hongcheng Mai, Jiankun Zang, Lingling Shen, Yusheng Zhang, Anding Xu
Hemorrhagic transformation (HT) is a serious complication that stimulates inflammation during reperfusion therapy after acute ischemic stroke. Rosuvastatin, a 3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, might improve the outcome of HT by inhibiting neuroinflammation. This study aimed to explore the protective effects of rosuvastatin against HT after recombinant tissue plasminogen activator (rt-PA) treatment in mice with experimental stroke via the attenuation of inflammation. A total of one hundred sixty-nine male BALB/c mice were used in the experiment...
2018: Frontiers in Cellular Neuroscience
Faleh Alqahtani, Ekram Ahmed Chowdhury, Raktima Bhattacharya, Behnam Noorani, Reza Mehvar, Ulrich Bickel
Among small, hydrophilic drug-like molecules, [14 C]sucrose has long been considered the gold standard for determination of blood-brain barrier (BBB) permeability. However, we have recently shown in rats that, compared with LC-MS/MS analysis of stable isotope (13 C) of sucrose, [14 C]sucrose significantly overestimates the brain tissue concentration and uptake of sucrose by a factor of 6-7. This discrepancy is due to the presence of small quantities of lipophilic impurities in [14 C]sucrose tracer solutions...
August 16, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Lindsay Joy Spielman, Deanna Lynn Gibson, Andis Klegeris
The number of bacterial cells living within the human body is approximately equal to, or greater than, the total number of human cells. This dynamic population of microorganisms, termed the human microbiota, resides mainly within the gastrointestinal tract. It is widely accepted that highly diverse and stable microbiota promote overall human health. Colonization of the gut with maladaptive and pathogenic microbiota, a state also known as dysbiosis, is associated with a variety of peripheral diseases ranging from type 2 diabetes mellitus to cardiovascular and inflammatory bowel disease...
August 13, 2018: Neurochemistry International
Dallan McMahon, Ethan Mah, Kullervo Hynynen
Focused ultrasound (FUS) and circulating microbubbles can induce a targeted and transient increase in blood-brain barrier permeability. While preclinical research has demonstrated the utility of FUS for efficacious drug deliver to the brain, there remain gaps in our knowledge regarding the long-term response of brain vasculature to this intervention. Previous work has demonstrated transcriptional changes in hippocampal microvessels following sonication that are indicative of the initiation of angiogenic processes...
August 15, 2018: Scientific Reports
Yixiang Xu, Jian Zhang, Huan Wang, Fei Mao, Keting Bao, Wenwen Liu, Jin Zhu, Xiaokang Li, Haiyan Zhang, Jian Li
Multifunctional agents aiming at cholinesterases (ChEs) and monoamine oxidases (MAOs) are promising therapy for Alzheimer's Disease (AD). Herein, a series of novel propargylamine-modified pyrimidinylthiourea derivatives (1-4) were designed and synthesized as dual inhibitors of ChEs and MAOs with other functions against AD. Most of these derivatives inhibited ChEs and MAOs with IC50 values in the micro- or nanomolar ranges. Compound 1c displayed the dual functional profile of targeting the AChE (IC50 = 0.032 ± 0...
August 15, 2018: ACS Chemical Neuroscience
Zhuang Wang, Hongbin Yang, Zengrui Wu, Tianduanyi Wang, Weihua Li, Yun Tang, Guixia Liu
Blood-Brain Barrier (BBB) as a part of absorption protects the central nervous system by separating the brain tissue from the bloodstream. In recent years, BBB permeability has become a critical issue in chemical ADMET (absorption, distribution, metabolism, excretion, and toxicity) prediction, but almost all models were built with imbalanced datasets, which caused high false positive rate. Therefore, in this study, we tried to solve the bias problem and built a reliable classification model with 2358 compounds...
August 15, 2018: ChemMedChem
Chandrani Nath, Vishnu Nayak Badavath, Abhishek Thakur, Gulberk Ucar, Orlando Acevedo, Mohd Usman Mohd Siddique, Venkatesan Jayaprakash
A series of 2-methoxy-4-(5-phenyl-4,5-dihydro-1 H -pyrazol-3-yl)phenol (pyrazoline) derivatives ( 2-6 ) have been synthesized and tested for human monoamine oxidase (hMAO) inhibitory activity. The most active derivative ( 2 ) behaved as a competitive hMAO-A inhibitor, with an inhibition constant value of 0.08 μM and a strong hMAO-A selectivity ( K i (hMAO-B)/ K i (hMAO-A) > 1751). In addition, 2 exhibited little to no cytotoxic effects up to a 25 μM concentration and provided the best blood-brain barrier permeability among the derivatives synthesized...
July 1, 2018: MedChemComm
G S M Sundaram, Kristen Binz, Vedica Sharma, Melany Yeung, Vijay Sharma
Thioflavin T (ThT), a positively charged heterocyclic small molecule, is a widely used fluorescent marker of amyloid pathophysiology to confirm the cause of death in post mortem brain tissue of Alzheimer's disease (AD) patients. Literature precedents indicate that current positron emission tomography (PET) agents, such as 11 C-PIB and 18 F-flutemetamol, share significant structural similarity with ThT, a lipophilic dye which does not traverse the blood-brain barrier (BBB) to enable the detection of Aβ plaques in vivo ...
June 1, 2018: MedChemComm
Yiwei Wang, Yinan Chen, Qin Zhou, Jiawen Xu, Qingqing Qian, Pengfei Ni, Yanning Qian
Recent research has revealed that uncontrolled chronic neuroinflammation is closely associated with diverse neurodegenerative diseases, by impairing blood-brain barrier (BBB) function and astrocytic reaction. Endoplasmic reticulum (ER) stress is conventionally linked to the loss of neuronal structure and function and should be widely attenuated. This notion has been questioned by recent experimental studies, which have shown that non-harmful levels of ER stress had numerous beneficial roles against neurodegeneration, including neuroprotection and inhibition of cytokine production...
2018: Frontiers in Cellular Neuroscience
Tomáš Zeman, El-Wui Loh, Daniel Čierný, Omar Šerý
Titanium dioxide (TiO2 ) has been vastly used commercially, especially as white pigment in paints, colorants, plastics, coatings, cosmetics. Certain industrial uses TiO2 in diameter <100 nm. There are three common exposure routes for TiO2 : (i) inhalation exposure, (ii) exposure via gastrointestinal tract, (iii) dermal exposure. Inhalation and gastrointestinal exposure appear to be the most probable ways of exposure, although nanoparticle (NP) penetration is limited. However, the penetration rate may increase substantially when the tissue is impaired...
September 2018: IET Nanobiotechnology
Wei Gao, Ying-Nan Ju, Jian-Feng Chen, Qiang Zhou, Chun-Yu Song, Yue-Zhen Wang, Hong-Ling Cao, Wan-Chao Yang
OBJECTIVE: Traumatic brain injury (TBI) is a devastating neurological injury, and remains as a major cause of death in the world. Secondary injury after TBI is associated with long-term disability in patients with TBI. The present study evaluated adrenomedullin (AM) on secondary injury and neurological functional outcome in rats after TBI. METHODS: Forty-eight SD rats were randomly assigned into three groups: sham, TBI and TBI+AM groups. TBI was induced by fluid percussion injury (FPI) and AM was intravenously injected...
August 7, 2018: World Neurosurgery
Mahsa Sarami Foroshani, Zeinab Sadat Sobhani, Mohammad Taghi Mohammadi, Masiha Aryafar
BACKGROUND: The present study aimed to examine the protective role of fullerenol nanoparticles against blood-brain barrier (BBB) interruption and brain edema during cerebral ischemia-reperfusion injury probably by reduction of interleukin-6 (IL-6) and matrix metalloproteinase-9 (MMP-9) transcription. METHODS: The male Wistar rats (weighting 280-320 g) were randomly assigned into four groups as follows: sham, control ischemic, pretreated ischemic, and posttreated ischemic groups...
August 6, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Jordi Pedragosa, Angélica Salas-Perdomo, Mattia Gallizioli, Roger Cugota, Francesc Miró-Mur, Ferran Briansó, Carles Justicia, Fernando Pérez-Asensio, Leonardo Marquez-Kisinousky, Xabier Urra, Anna Gieryng, Bozena Kaminska, Angel Chamorro, Anna M Planas
The central nervous system (CNS) contains several types of immune cells located in specific anatomic compartments. Macrophages reside at the CNS borders surrounding the brain vessels, in leptomeningeal spaces and the choroid plexus, where they interact with the vasculature and play immunological surveillance and scavenging functions. We investigated the phenotypic changes and role of these macrophages in response to acute ischemic stroke. Given that CD163 expression is a hallmark of perivascular and meningeal macrophages in the rat and human brain, we isolated CD163+ brain macrophages by fluorescence activated cell sorting...
August 9, 2018: Acta Neuropathologica Communications
Minji Bang, Onjeon Ryu, Do Gyeong Kim, Darine Froy Mabunga, Kyu Suk Cho, Yujeong Kim, Seol-Heui Han, Kyoung Ja Kwon, Chan Young Shin
Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation...
August 10, 2018: Biomolecules & Therapeutics
Pian Gong, Zhan Zhang, Changlin Zou, Qi Tian, Xuemei Chen, Michael Hong, Xi Liu, Qianxue Chen, Zhou Xu, Mingchang Li, Jian Wang
Ischemia/reperfusion (I/R) injuries commonly lead to breakdown of the blood-brain barrier (BBB).Restoration of the BBB can relieve neurologic damage caused by I/R injuries. The Hippo/YAP signaling pathway mediates cell proliferation, regulated cell death, and differentiation in various organisms and has been shown to participate in the restoration of the heart after I/R. In this study, we investigated whether the Hippo/YAP pathway plays a role in I/R injury in brain, especially in regard to I/R-induced BBB breakdown...
August 6, 2018: Behavioural Brain Research
Sena Iwata, Takahiko Imai, Masamitsu Shimazawa, Takashi Ishibashi, Masahiro Hayashi, Hideaki Hara, Shinsuke Nakamura
Astaxanthin is beneficial for human health and is used as a dietary supplement. The present study was performed in order to examine the protective effects of the astaxanthin derivative, adonixanthin, against cell death caused by hemoglobin, collagenase, lipopolysaccharide, and hydrogen peroxide, which are associated with hemorrhagic brain injury. In an in vitro study, adonixanthin exerted cytoprotective effects against each type of damage, and its effects were stronger than those of astaxanthin. The increased production of reactive oxygen species in human brain endothelial cells in the hemoglobin treatment group was inhibited by adonixanthin...
August 6, 2018: Brain Research
E Vendel, V Rottschäfer, E C M de Lange
The development of drugs that target the brain is very challenging. A quantitative understanding is needed of the complex processes that govern the concentration-time profile of a drug (pharmacokinetics) within the brain. So far, there are no studies on predicting the drug concentration within the brain that focus not only on the transport of drugs to the brain through the blood-brain barrier (BBB), but also on drug transport and binding within the brain. Here, we develop a new model for a 2D square brain tissue unit, consisting of brain extracellular fluid (ECF) that is surrounded by the brain capillaries...
August 8, 2018: Bulletin of Mathematical Biology
Tamara K Stevenson, Daniel A Lawrence
Tissue plasminogen activator (tPA) is an immediate-early gene important for regulating physiological processes like synaptic plasticity and neurovascular coupling. It has also been implicated in several pathological processes including blood-brain barrier (BBB) permeability, seizure progression, and stroke. These varied reports suggest that tPA is a pleiotropic mediator whose actions are highly compartmentalized in space and time. The specific localization of tPA, therefore, can provide useful information about its function...
July 2018: ENeuro
Siti R Yusof, Mahathir Mohd Uzid, Eng-Huat Teh, Nur Aziah Hanapi, Mazlin Mohideen, Ahmad Saifuddin Mohamad Arshad, Mohd Nizam Mordi, Irena Loryan, Margareta Hammarlund-Udenaes
Mitragyna speciosa is reported to be beneficial for the management of chronic pain and opioid withdrawal in the evolving opioid epidemic. Data on the blood-brain barrier (BBB) transport of mitragynine and 7-hydroxymitragynine, the active compounds of the plant, are still lacking and inconclusive. Here, we present for the first time the rate and the extent of mitragynine and 7-hydroxymitragynine transport across the BBB, with an investigation of their post-BBB intra-brain distribution. We utilized an in vitro BBB model to study the rate of BBB permeation of the compounds and their interaction with efflux transporter P-glycoprotein (P-gp)...
August 8, 2018: Addiction Biology
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