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Blood brain barrier

Nebojsa Mihajlica, Christer Betsholtz, Margareta Hammarlund-Udenaes
Pericytes are perivascular cells that play important roles in the regulation of the blood-brain barrier (BBB) properties. Pericyte-deficiency causes compromised BBB integrity and increase in permeability to different macromolecules mainly by upregulated transcytosis. The aim of the present study was to investigate pericyte involvement in the extent of small-molecular drug transport across the BBB. This was performed with five compounds: diazepam, digoxin, levofloxacin, oxycodone and paliperidone. Compounds were administered at low doses via subcutaneous injections as a cassette (simultaneously) to pericyte-deficient Pdgfbret/ret mice and corresponding WT controls...
June 19, 2018: European Journal of Pharmaceutical Sciences
Vimala N Bharadwaj, Rachel K Rowe, Jordan Harrison, Chen Wu, Trent R Anderson, Jonathan Lifshitz, P David Adelson, Vikram D Kodibagkar, Sarah E Stabenfeldt
Clinically, traumatic brain injury (TBI) results in complex heterogeneous pathology that cannot be recapitulated in single pre-clinical animal model. Therefore, we focused on evaluating utility of nanoparticle (NP)-based therapeutics following three diffuse-TBI models: mild-closed-head injury (mCHI), repetitive-mCHI and midline-fluid percussion injury (FPI). We hypothesized that NP accumulation after diffuse TBI correlates directly with blood-brain-barrier permeability. Mice received PEGylated-NP cocktail (20-500nm) (intravenously) after single- or repetitive-(1 impact/day, 5 consecutive days) CHI (immediately) and midline-FPI (1h, 3h and 6h)...
June 19, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Dong-Suk Kim, Poojya Anantharam, Andrea Hoffmann, Mitchell L Meade, Nadja Grobe, Jeffery M Gearhart, Elizabeth M Whitley, Belinda Mahama, Wilson K Rumbeiha
Acute exposure to high concentrations of H2 S causes severe brain injury and long-term neurological disorders, but the mechanisms involved are not known. To better understand the cellular and molecular mechanisms involved in acute H2 S-induced neurodegeneration we used a broad-spectrum proteomic analysis approach to identify key molecules and molecular pathways involved in the pathogenesis of acute H2 S-induced neurotoxicity and neurodegeneration. Mice were subjected to acute inhalation exposure of up to750 ppm of H2 S...
June 19, 2018: Toxicology and Applied Pharmacology
Qunqun Bao, Ping Hu, Yingying Xu, Tiansheng Cheng, Chenyang Wei, Limin Pan, Jianlin Shi
Cerebral vasculature and neuronal networks will be largely destroyed due to the oxidative damages by over-produced reactive oxygen species (ROS) during stroke, accompanied by the symptoms of ischemic injury and blood-brain barrier (BBB) disruption. Ceria nanoparticles, acting as an effective and recyclable ROS scavenger, have been showing high effectiveness in neuroprotection. However, the brain access of nanoparticles can only be achieved by targeting the damaged area of BBB, leading to the disrupted BBB unprotected and turbulence of microenvironment in brain...
June 22, 2018: ACS Nano
Sern Wei Yeoh, Alex C N Holmes, Michael M Saling, Ian P Everall, Amanda J Nicoll
Patients with chronic hepatitis C virus (HCV) infection experience a range of symptoms including depression, fatigue and neurocognitive deficits, impairing quality of life. Depression, in particular, may be reactive to increased psychosocial stress, and the physical symptoms of advanced HCV or associated comorbidities. However, even patients at an early stage of HCV infection, with minimal hepatic inflammation or comorbidities, report more depressive symptoms and fatigue than the general population. Similarly, specific neurocognitive deficits occur in early stage HCV infection and are independent of the presence of depression or encephalopathy...
June 21, 2018: Hepatology International
Kasper Bendix Johnsen, Martin Bak, Paul Joseph Kempen, Fredrik Melander, Annette Burkhart, Maj Schneider Thomsen, Morten Schallburg Nielsen, Torben Moos, Thomas Lars Andresen
Rationale: The ability to treat invalidating neurological diseases is impeded by the presence of the blood-brain barrier (BBB), which inhibits the transport of most blood-borne substances into the brain parenchyma. Targeting the transferrin receptor (TfR) on the surface of brain capillaries has been a popular strategy to give a preferential accumulation of drugs or nanomedicines, but several aspects of this targeting strategy remain elusive. Here we report that TfR-targeted gold nanoparticles (AuNPs) can accumulate in brain capillaries and further transport across the BBB to enter the brain parenchyma...
2018: Theranostics
Jiangman Song, Lu Yang, Di Nan, Qihua He, You Wan, Huailian Guo
Chronic cerebral hypoperfusion is one of the fundamental pathological causes of brain disease such as vascular dementia. Exploration of effective treatments for this is of great interest. Histidine has been reported to be effective in anti-apoptosis, antioxidant, and against excitotoxicity. In the present study, we aim to investigate whether histidine could have a therapeutic effect on the impairments induced by chronic cerebral hypoperfusion. Cerebral hypoperfusion model was established through bilateral common carotid arteries stenosis (BCAS) operation in Tie2-GFP mice...
2018: Frontiers in Physiology
Keren Kaufman-Francis, Julianne T Djordjevic, Pierre-Georges Juillard, Sophie Lev, Desmarini Desmarini, Georges E R Grau, Tania C Sorrell
The innate immune system is the primary defense against cryptococcal infection, but paradoxically it promotes infection of the central nervous system. We performed a detailed longitudinal study of neurocryptococcosis in normal, chimeric, green fluorescent protein phagocyte-positive mice and phagocyte-depleted mice and interrogated the central nervous system innate immune response to Cryptococcus neoformans H99 using confocal microscopy, histology, flow cytometry, and quantification of brain cytokine/chemokines and fungal burdens...
June 18, 2018: American Journal of Pathology
Jianping Wang, Di Zhang, Xiaojie Fu, Lie Yu, Zhengfang Lu, Yufeng Gao, Xianliang Liu, Jiang Man, Sijia Li, Nan Li, Xuemei Chen, Michael Hong, Qingwu Yang, Jian Wang
BACKGROUND: At low levels, carbon monoxide (CO) has been shown to have beneficial effects on multiple organs and tissues through its potential anti-inflammatory, anti-apoptotic, and anti-proliferative properties. However, the effect of CO-releasing molecule (CORM)-3, a water-soluble CORM, on ischemic stroke and its mechanism of action are still unclear. METHODS: We investigated the role of CORM-3 in the mouse model of transient middle cerebral artery occlusion (tMCAO)...
June 21, 2018: Journal of Neuroinflammation
Pau Comajoan, Carme Gubern, Gemma Huguet, Joaquín Serena, Elisabet Kádár, Mar Castellanos
Thrombolysis with recombinant tissue plasminogen activator (rt-PA) is the only pharmacological approved treatment for ischemic stroke, despite its associated increasing risk of hemorrhagic transformation. Since many of rt-PA effects in blood-brain barrier (BBB) are not well characterized, the study of protein changes in BBB cells after rt-PA administration may help to understand its adverse effects. Our aim was to analyze protein levels of four commonly used housekeeping proteins: β-Actin, α-Tubulin, GAPDH and HPRT in bEnd...
June 18, 2018: Journal of Proteomics
Katharina Hammerbacher, Katharina Görtemaker, Christine Knies, Eugenia Bender, Gabriel A Bonaterra, Helmut Rosemeyer, Ralf Kinscherf
Two series of nucleolipids, (i) O-2',3'-heptanylidene- as well as O-2',3'-undecanylidene ketals of 6 ß-D-ribonucleosides (type A) and partly N-farnesyl derivatives thereof (type B) were prepared in a combinatorial manner. All novel compounds were characterized by elemental analysis and/or ESI mass spectrometry and by UV-, 1 H-, and 13 C-NMR spectroscopy. Conformational parameters of the nucleosides and nucleolipids were calculated from various 3 J(H,H), 3 J(1 H,13 C) and 5 J(F,H) coupling constants. For a drug profiling the parent nucleosides and their lipophilic derivatives were studied with respect to their distribution (log P) between water and n-octanol as well as water and cyclohexane...
June 21, 2018: Chemistry & Biodiversity
Guanglei Fu, Hua Wang, Youli Cai, Hui Zhao, Wenjun Fu
Objective: Intracerebral hemorrhage (ICH) is one of the most common acute cerebrovascular diseases with high mortality. Numerous studies have shown that inflammatory response played an important role in ICH-induced brain injury. Theaflavin (TF) extracted from black tea has various biological functions including anti-inflammatory activity. In this study, we investigated whether TF could inhibit ICH-induced inflammatory response in rats and explored its mechanism. Materials and methods: ICH rat models were induced with type VII collagenase and pretreated with TF by gavage in different doses (25 mg/kg-100 mg/kg)...
2018: Drug Design, Development and Therapy
Austin Horton, Kevin Nash, Ethel Tackie-Yarboi, Alexander Kostrevski, Adam Novak, Aparna Raghavan, Jatin Tulsulkar, Qasim Alhadidi, Nathan Wamer, Bryn Langenderfer, Kalee Royster, Maxwell Ducharme, Katelyn Hagood, Megan Post, Zahoor A Shah, Isaac T Schiefer
No abstract text is available yet for this article.
June 21, 2018: Journal of Medicinal Chemistry
Yung-Hao Tsou, Xue-Qing Zhang, He Zhu, Sahla Syed, Xiaoyang Xu
No abstract text is available yet for this article.
June 2018: Small
Yu N Rushkevich, I D Pashkouskaya, S A Likhachev
AIM: To determine concentrations of neurospecific enolase (NSE) and S100b protein in bloodserum and cerebrospinal fluid (CSF) in patients with amyotrophic lateral sclerosis (ALS) with different forms (onset) and duration of ALS. MATERIAL AND METHODS: Concentrations of NSE and S100b in serum and CSF were studied in 86 patients with different forms and duration of ALS. RESULTS AND CONCLUSION: Concentrations of NSE and S100b protein in CSF were significantly higher in the group of patients with bulbar form and in the group with duration of disease less than 1 year compared to the control group...
2018: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
John G Hanly, Elizabeth Kozora, Steven Beyea, Julius Birnbaum
The American College of Rheumatology (ACR) case definitions for 19 neuropsychiatric syndromes constitute a comprehensive classification of nervous system events in SLE patients. However, additional strategies are needed to determine whether a neurological syndrome is attributable to SLE versus a competing co-morbidity. Cognitive function is a clinical surrogate of overall brain health with applications in both diagnosis and determination of clinical outcomes. Ischemic and inflammatory mechanisms are both key components of the immunopathogenesis of NPSLE, including abnormalities of the blood-brain-barrier and autoantibody mediated production of pro-inflammatory cytokines...
June 21, 2018: Arthritis & Rheumatology
Minghang Li, Xiaocui Tian, Ruidi An, Mei Yang, Qian Zhang, Fei Xiang, Hailin Liu, Yuchun Wang, Lu Xu, Zhi Dong
The original version of this article unfortunately contained a mistake. The affiliation of the author Lu Xu has been submitted and published incorrectly and has been corrected with the erratum.
June 20, 2018: Neurochemical Research
Mark R Griffiths, Marina Botto, B Paul Morgan, J W Neal, P Gasque
Microglia and non-professional immune cells (endothelial cells, neurons) participate in the recognition and removal of pathogens and tissue-debris in the injured CNS through major pro-inflammatory processes. However, the mechanisms involved in regulating these responses remain ill-characterised. We herein show that CD93 also known as complement C1qRp/AA4 stem cell marker has an important role in the regulation of inflammatory processes. The role of CD93 was evaluated in two models of neuroinflammation. We used the MOG-experimental autoimmune encephalomyelitis (EAE) model and the antibody-dependent EAE (ADEAE) which were induced in wild type and CD93 knockout mice...
June 20, 2018: Immunology
Tsung-Yun Wong, Ming-Shian Tsai, Lih-Ching Hsu, Shu-Wha Lin, Pi-Hui Liang
Apigenin, a flavone abundant in parsley and celery, is known to act on several CNS receptors, but its very poor water solubility (< 0.001 mg/mL) impedes its absorption in vivo and prevents clinical use. Herein, apigenin was directly conjugated with glycine, L-phenylalanine, and L-lysine to give the corresponding carbamate derivatives, all of which were much more soluble than apigenin itself (0.017, 0.018, and 0.13 mg/mL, respectively). The Lys-apigenin carbamate 10 had a temporary sedative effect on the mice within five minutes of intraperitoneal administration (single dose of 0...
June 20, 2018: Journal of Agricultural and Food Chemistry
Jacob R Greenmyer, Robert A Gaultney, Catherine A Brissette, John A Watt
The Lyme disease causing bacterium Borrelia burgdorferi has an affinity for the central nervous system (CNS) and has been isolated from human cerebral spinal fluid by 18 days following Ixodes scapularis tick bite. Signaling from resident immune cells of the CNS could enhance CNS penetration by B. burgdorferi and activated immune cells through the blood brain barrier resulting in multiple neurological complications, collectively termed neuroborreliosis. The ensuing symptoms of neurological impairment likely arise from a glial-driven, host inflammatory response to B...
2018: Frontiers in Microbiology
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