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https://www.readbyqxmd.com/read/28646881/heme-molecule-functions-as-an-endogenous-agonist-of-astrocyte-tlr2-to-contribute-to-secondary-brain-damage-after-intracerebral-hemorrhage
#1
Hyunjung Min, Boomin Choi, Yong Ho Jang, Ik-Hyun Cho, Sung Joong Lee
Toll-like receptor 2 (TLR2) was recently shown to contribute to secondary brain damage after intracerebral hemorrhage (ICH), although the molecular mechanisms of this contribution are elusive. In this study, we tested the hypothesis that hemin functions as a TLR2 endogenous agonist, causing proinflammatory astrocyte activation and secondary brain damage after ICH. Hemin administration to the mouse brain striatum induced ICH injury and neurological deficits, however, the brain injury volume and neurological deficits due to hemin injection were significantly reduced in TLR2 knock-out (KO) mice...
June 24, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28646795/offsetting-the-impact-of-smoking-and-e-cigarette-vaping-on-the-cerebrovascular-system-and-stroke-injury-is-metformin-a-viable-countermeasure
#2
Mohammad A Kaisar, Heidi Villalba, Shikha Prasad, Taylor Liles, Ali Ehsan Sifat, Ravi K Sajja, Thomas J Abbruscato, Luca Cucullo
Recently published in vitro and in vivo findings strongly suggest that BBB impairment and increased risk for stroke by tobacco smoke (TS) closely resemble that of type-2 diabetes (2DM) and develop largely in response to common key modulators such oxidative stress (OS), inflammation and alterations of the endogenous antioxidative response system (ARE) regulated by the nuclear factor erythroid 2-related factor (Nrf2). Preclinical studies have also shown that nicotine (the principal e-liquid's ingredient used in e-cigarettes) can also cause OS, exacerbation of cerebral ischemia and secondary brain injury...
June 17, 2017: Redox Biology
https://www.readbyqxmd.com/read/28645333/sac-1004-a-vascular-leakage-blocker-reduces-cerebral-ischemia-reperfusion-injury-by-suppressing-blood-brain-barrier-disruption-and-inflammation
#3
Haiying Zhang, Joon Ha Park, Sony Maharjan, Jeong Ae Park, Kyu-Sung Choi, Hyojin Park, Yoonjeong Jeong, Ji Hyeon Ahn, In Hye Kim, Jae-Chul Lee, Jeong Hwi Cho, In-Kyu Lee, Choong Hyun Lee, In Koo Hwang, Young-Myeong Kim, Young-Ger Suh, Moo-Ho Won, Young-Guen Kwon
BACKGROUND: Blood-brain barrier (BBB) breakdown and inflammation are critical events in ischemic stroke, contributing to aggravated brain damage. The BBB mainly consists of microvascular endothelial cells sealed by tight junctions to protect the brain from blood-borne substances. Thus, the maintenance of BBB integrity may be a potential target for neuroprotection. Sac-1004, a pseudo-sugar derivative of cholesterol, enhances the endothelial barrier by the stabilization of the cortical actin ring...
June 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28642177/protective-functions-of-pj34-a-parp-inhibitor-is-related-to-down-regulation-of-calpain-and-nf-%C3%AE%C2%BAb-in-a-mouse-model-of-tbi
#4
Xiaogang Tao, Xuetao Chen, Zonggang Hou, Shuyu Hao, Baiyun Liu
OBJECTIVES: Poly(ADP-ribose) polymerase (PARP), calpain, and nuclear factor-κB (NF-κB) are reported to participate in inflammatory reactions in pathological conditions and are involved in traumatic brain injury. The objective of this study was to investigate whether PARP participated in inflammation related to calpain and NF-κB in a mouse model of controlled cortical impact (CCI). METHODS: PJ34 (10 mg/kg), a selective PARP inhibitor, was administered intraperitoneally 5 min and 8 h after experimental CCI...
June 19, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28641606/solving-the-challenge-of-the-blood-brain-barrier-to-treat-infections-caused-by-trypanosoma-evansi-evaluation-of-nerolidol-loaded-nanospheres-in-mice
#5
Matheus D Baldissera, Carine F Souza, Aline A Boligon, Thirssa H Grando, Mariângela F DE Sá, Aleksandro S DA Silva, Lenita M Stefani, Bernardo Baldisserotto, Silvia G Monteiro
Despite significant advances in therapies against Trypanosoma evansi, its effective elimination from the central nervous system (CNS) remains a difficult task. The incapacity of trypanocidal drugs to cross the blood-brain barrier (BBB) after systemic administrations makes the brain the main refuge area for T. evansi. Nanotechnology is showing great potential to improve drug efficacy, such as nerolidol-loaded nanospheres (N-NS). Thus, the aim of this study was to investigate whether the treatment with N-NS was able to cross the BBB and to eliminate T...
June 23, 2017: Parasitology
https://www.readbyqxmd.com/read/28641198/combined-computational-experimental-approach-to-predict-blood-brain-barrier-bbb-permeation-based-on-green-salting-out-thin-layer-chromatography-supported-by-simple-molecular-descriptors
#6
Krzesimir Ciura, Mariusz Belka, Piotr Kawczak, Tomasz Bączek, Michał J Markuszewski, Joanna Nowakowska
The objective of this paper is to build QSRR/QSAR model for predicting the blood-brain barrier (BBB) permeability. The obtained models are based on salting-out thin layer chromatography (SOTLC) constants and calculated molecular descriptors. Among chromatographic methods SOTLC was chosen, since the mobile phases are free of organic solvent. As consequences, there are less toxic, and have lower environmental impact compared to classical reserved phases liquid chromatography (RPLC). During the study three stationary phase silica gel, cellulose plates and neutral aluminum oxide were examined...
June 3, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28641010/alpha-mangostin-reverses-multidrug-resistance-by-attenuating-the-function-of-the-multidrug-resistance-linked-abcg2-transporter
#7
Chung-Pu Wu, Sung-Han Hsiao, Megumi Murakami, Yu-Jen Lu, Yan-Qing Li, Yang-Hui Huang, Tai-Ho Hung, Suresh V Ambudkar, Yu-Shan Wu
The ATP-binding cassette (ABC) drug transporter ABCG2 can actively efflux a wide variety of chemotherapeutic agents out of cancer cells and subsequently reduce the intracellular accumulation of these drugs. Therefore, the overexpression of ABCG2 often contributes to the development of multidrug resistance (MDR) in cancer cells, which is one of the major obstacles to successful cancer chemotherapy. Moreover, ABCG2 is highly expressed in various tissues including the intestine and blood-brain barrier (BBB), limiting the absorption and bioavailability of many therapeutic agents...
June 22, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28640596/drug-target-kinetics-in-drug-discovery
#8
Peter J Tonge
The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation...
June 22, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28639394/transferrin-conjugated-magnetic-dextran-spermine-nanoparticles-for-targeted-drug-transport-across-blood-brain-barrier
#9
Maryam Ghadiri, Ebrahim Vasheghani-Farahani, Fatemeh Atyabi, Farzad Kobarfard, Farzaneh Mohamadyar-Toupkanlou, Hossein Hosseinkhani
Application of many vital hydrophilic medicines have been restricted by blood-brain barrier (BBB) for treatment of brain diseases. In this study, a targeted drug delivery system based on dextran-spermine biopolymer was developed for drug transport across BBB. Drug loaded magnetic dextran-spermine nanoparticles (DS-NPs) were prepared via ionic gelation followed by transferrin (Tf) conjugation as targeting moiety. The characteristics of Tf conjugated nanoparticles (TDS-NPs) were analyzed by different methods and their cytotoxicity effects on U87MG cells were tested...
June 22, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28638340/neurologically-potent-molecules-from-crataegus-oxyacantha-isolation-anticholinesterase-inhibition-and-molecular-docking
#10
Mumtaz Ali, Sultan Muhammad, Muhammad R Shah, Ajmal Khan, Umer Rashid, Umar Farooq, Farhat Ullah, Abdul Sadiq, Muhammad Ayaz, Majid Ali, Manzoor Ahmad, Abdul Latif
Crataegus oxyacantha is an important herbal supplement and famous for its antioxidant potential. The antioxidant in combination with anticholinesterase activity can be considered as an important target in the management of Alzheimer's disease. The compounds isolated from C. oxyacantha were evaluated for cholinesterases inhibitory activity using Ellman's assay with Galantamine as standard drug. Total of nine (1-9) compounds were isolated. Compounds 1 and 2 were isolated for the first time from natural source...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28637381/role-of-caspase-3-mediated-apoptosis-in-chronic-caspase-3-cleaved-tau-accumulation-and-blood-brain-barrier-damage-in-the-corpus-callosum-after-traumatic-brain-injury-in-rats
#11
Olena Glushakova, Andriy O Glushakov, Cesar Borlongan, Alex Valadka, Ronald L Hayes, Alexander V Glushakov
Traumatic brain injury (TBI) may be a significant risk factor for development of neurodegenerative disorders such as chronic traumatic encephalopathy (CTE), post-traumatic epilepsy (PTE), and Alzheimer's (AD) and Parkinson's (PD) diseases. Chronic TBI is associated with several pathological features that are also characteristic of neurodegenerative diseases, including tau pathologies, caspase-3-mediated apoptosis, neuroinflammation, and microvascular alterations. The goal of this study was to evaluate changes following TBI in cleaved-caspase-3 and caspase-3-cleaved tau truncated at Asp421 and their relationships to cellular markers potentially associated with inflammation and blood-brain (BBB) barrier damage...
June 22, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28636879/delineating-neuroinflammation-parasite-cns-invasion-and-blood-brain-barrier-dysfunction-in-an-experimental-murine-model-of-human-african-trypanosomiasis
#12
Jean Rodgers, Barbara Bradley, Peter G E Kennedy
Although Trypanosoma brucei spp. was first detected by Aldo Castellani in CSF samples taken from sleeping sickness patients over a century ago there is still a great deal of debate surrounding the timing, route and effects of transmigration of the parasite from the blood to the CNS. In this investigation, we have applied contrast-enhance magnetic resonance imaging (MRI) to study the effects of trypanosome infection on the blood-brain barrier (BBB) in the well-established GVR35 mouse model of sleeping sickness...
June 18, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28635335/a-novel-synergetic-targeting-strategy-for-glioma-therapy-employing-borneol-combination-with-angiopep-2-modified-dox-loaded-pamam-dendrimer
#13
Shunping Han, Hongyue Zheng, Yanping Lu, Yue Sun, Anhao Huang, Weidong Fei, Xiaowei Shi, Xiuling Xu, Jingjing Li, Fanzhu Li
Glioma is the most common primary malignant brain tumor and the effect of chemotherapy is hampered by low permeability across the blood-brain-barrier (BBB). Borneol is a time-honored 'Guide' drug in traditional Chinese medicine and has been proved to be capable of promoting free drugs into the brain efficiently, but there are still risks that free drugs, especially anti-glioma drugs, may be disassembled and metabolized before penetrating the BBB and caused the whole brain distribution. The purpose of this paper was to investigate whether borneol intervention could facilitate the BBB penetration and assist glioma treatment by combining with doxorubicin (DOX) loaded PAMAM dendrimers drug delivery system modified with Angiopep-2 (a ligand of the low-density lipoprotein receptor-related protein, which overexpress both in the BBB and gliomas)...
June 21, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28634726/connexin-channels-at-the-glio-vascular-interface-gatekeepers-of-the-brain
#14
Marijke De Bock, Luc Leybaert, Christian Giaume
Neuronal survival, electrical signaling and synaptic activity require a well-balanced micro-environment in the central nervous system. This is achieved by the blood-brain barrier (BBB), an endothelial barrier situated in the brain capillaries, that controls near-to-all passage in and out of the brain. The endothelial barrier function is highly dependent on signaling interactions with surrounding glial, neuronal and vascular cells, together forming the neuro-glio-vascular unit. Within this functional unit, connexin (Cx) channels are of utmost importance for intercellular communication between the different cellular compartments...
June 20, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28634084/drug-delivery-to-melanoma-brain-metastases-can-current-challenges-lead-to-new-opportunities
#15
Gautham Gampa, Shruthi Vaidhyanathan, Jann N Sarkaria, William F Elmquist
Melanoma has a high propensity to metastasize to the brain, and patients with melanoma brain metastases (MBM) have an extremely poor prognosis. The recent approval of several molecularly-targeted agents (e.g., BRAF, MEK inhibitors) and biologics (anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies) has brought new hope to patients suffering from this formerly untreatable and lethal disease. Importantly, there have been recent reports of success in some clinical studies examining the efficacy of both targeted agents and immunotherapies that show similar response rates in both brain metastases and extracranial disease...
June 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28633994/t-lymphocytes-infiltration-promotes-blood-brain-barrier-injury-after-experimental-intracerebral-hemorrhage
#16
Xuan Zhang, Wei Liu, Jichao Yuan, Haitao Zhu, Yang Yang, Zexian Wen, Yaxing Chen, Lan Li, Jiangkai Lin, Hua Feng
T lymphocytes migrate into the brain after intracerebral hemorrhage (ICH) and promote cerebral inflammation, thus exacerbating neuronal injury. However, the relationship between of T lymphocytes infiltration and blood-brain barrier (BBB) injury after ICH has not been clarified. In this study, we investigated the spatial-temporal distribution of infiltrating T lymphocytes after ICH in C57BL/6 mice by immunofluorescence and flow cytometry, and the accompanying change rules of BBB permeability were detected by Evans blue dye leakage and tight junction protein expression...
June 17, 2017: Brain Research
https://www.readbyqxmd.com/read/28632993/the-role-of-small-gtpases-and-epac-rap-signaling-in-the-regulation-of-the-blood-brain-and-blood-retinal-barriers
#17
Carla J Ramos, David A Antonetti
Maintenance and regulation of the vascular endothelial cell junctional complex is critical for proper barrier function of the blood-brain barrier (BBB) and the highly related blood-retinal barrier (BRB) that help maintain proper neuronal environment. Recent research has demonstrated that the junctional complex is actively maintained and can be dynamically regulated. Studies focusing on the mechanisms of barrier formation, maintenance, and barrier disruption have been of interest to understanding development of the BBB and BRB and identifying a means for therapeutic intervention for diseases ranging from brain tumors and dementia to blinding eye diseases...
June 9, 2017: Tissue Barriers
https://www.readbyqxmd.com/read/28630485/acute-administration-of-catalase-targeted-to-icam-1-attenuates-neuropathology-in-experimental-traumatic-brain-injury
#18
Evan M Lutton, Roshanak Razmpour, Allison M Andrews, Lee Anne Cannella, Young-Jin Son, Vladimir V Shuvaev, Vladimir R Muzykantov, Servio H Ramirez
Traumatic brain injury (TBI) contributes to one third of injury related deaths in the US. Treatment strategies for TBI are supportive, and the pathophysiology is not fully understood. Secondary mechanisms of injury in TBI, such as oxidative stress and inflammation, are points at which intervention may reduce neuropathology. Evidence suggests that reactive oxygen species (ROS) propagate blood-brain barrier (BBB) hyperpermeability and inflammation following TBI. We hypothesized that targeted detoxification of ROS may improve the pathological outcomes of TBI...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28629814/abcb1a-p-glycoprotein-limits-brain-exposure-of-the-anticancer-drug-candidate-seliciclib-in-vivo-in-adult-mice
#19
Franciska Erdő, Ildikó Nagy, Beáta Tóth, Annamária Bui, Éva Molnár, Zoltán Tímár, Rémi Magnan, Peter Krajcsi
Seliciclib displayed limited brain exposure in vivo in adult rats with mature blood-brain barrier (BBB). Selicilib was shown to be a specific substrate of human ABCB1 in vitro. To demonstrate that ABCB1/Abcb1 can limit brain exposure in vivo in mice we are showing that seliciclib is a substrate of mouse Abcb1a, the murine ABCB1 ortholog expressed in the BBB as LLC-PK-Abcb1a cells displayed an efflux ratio (ER) of 15.31±3.54 versus an ER of 1.44±0.10 in LLC-PK1-mock cells. Additionally, in the presence of LY335979, an ABCB1/Abcb1a specific inhibitor, the observed ER for seliciclib in the LLC-PK1-mMdr1a cells decreased to 1...
June 16, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28629519/erythropoietin-endogenous-protection-of-ischemic-brain
#20
Robert T Mallet, Myoung-Gwi Ryou
The human brain requires uninterrupted delivery of blood-borne oxygen and nutrients to sustain its function. Focal ischemia, particularly, ischemic stroke, and global ischemia imposed by cardiac arrest disrupt the brain's fuel supply. The resultant ATP depletion initiates a complex injury cascade encompassing intracellular Ca(2+) overload, glutamate excitotoxicity, oxido-nitrosative stress, extracellular matrix degradation, and inflammation, culminating in neuronal and astroglial necrosis and apoptosis, neurocognitive deficits, and even death...
2017: Vitamins and Hormones
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