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[PMID]: 29427702
[Au] Autor:Taccola C; Cartot-Cotton S; Valente D; Barneoud P; Aubert C; Boutet V; Gallen F; Lochus M; Nicolic S; Dodacki A; Smirnova M; Cisternino S; Declèves X; Bourasset F
[Ad] Address:Pharmacokinetics, Dynamics and Metabolism, Translational Medicine & Early Development, Sanofi, France; Variabilité de Réponse aux Psychotropes, Inserm, U1144, Paris F-75006, France; Faculté de Pharmacie de Paris, Université Paris Descartes, UMR-S 1144, Paris F-75006, France; Université Paris Did
[Ti] Title:High brain distribution of a new central nervous system drug candidate despite its P-glycoprotein-mediated efflux at the mouse blood-brain barrier.
[So] Source:Eur J Pharm Sci;117:68-79, 2018 Feb 07.
[Is] ISSN:1879-0720
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Efficacy of drugs aimed at treating central nervous system (CNS) disorders rely partly on their ability to cross the cerebral endothelium, also called the blood-brain barrier (BBB), which constitutes the main interface modulating exchanges of compounds between the brain and blood. In this work, we used both, conventional pharmacokinetics (PK) approach and in situ brain perfusion technique to study the blood and brain PK of PKRinh, an inhibitor of the double-stranded RNA-dependent protein kinase (PKR) activation, in mice. PKRinh showed a supra dose-proportional blood exposure that was not observed in the brain, and a brain to blood AUC ratio of unbound drug smaller than 1 at all tested doses. These data suggested the implication of an active efflux at the BBB. Using in situ brain perfusion technique, we showed that PKRinh has a very high brain uptake clearance which saturates with increasing concentrations. Fitting the data to a Michaelis-Menten equation revealed that PKRinh transport through the BBB is composed of a passive unsaturable flux and an active saturable protein-mediated efflux with a k of ≅ 3 µM. We were able to show that the ATP-binding cassette (ABC) transporter P-gp (Abcb1), but not Bcrp (Abcg2), was involved in the brain to blood efflux of PKRinh. At the circulating PKRinh concentrations of this study, the P-gp was not saturated, in accordance with the linear brain PKRinh PK. Finally, PKRinh had high brain uptake clearance (14 µl/g/s) despite it is a good P-gp substrate (P-gp Efflux ratio ≅ 3.6), and reached similar values than the cerebral blood flow reference, diazepam, in P-gp saturation conditions. With its very unique brain transport properties, PKRinh improves our knowledge about P-gp-mediated efflux across the BBB for the development of new CNS directed drugs.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 36610 MEDLINE  
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[PMID]: 29360998
[Au] Autor:Tagge CA; Fisher AM; Minaeva OV; Gaudreau-Balderrama A; Moncaster JA; Zhang XL; Wojnarowicz MW; Casey N; Lu H; Kokiko-Cochran ON; Saman S; Ericsson M; Onos KD; Veksler R; Senatorov VV; Kondo A; Zhou XZ; Miry O; Vose LR; Gopaul KR; Upreti C; Nowinski CJ; Cantu RC; Alvarez VE; Hildebrandt AM; Franz ES; Konrad J; Hamilton JA; Hua N; Tripodis Y; Anderson AT; Howell GR; Kaufer D; Hall GF; Lu KP; Ransohoff RM; Cleveland RO; Kowall NW; Stein TD; Lamb BT; Huber BR; Moss WC; Friedman A; Stanton PK; McKee AC; Goldstein LE
[Ad] Address:Molecular Aging and Development Laboratory, Boston University School of Medicine, Boston, MA 02118, USA.
[Ti] Title:Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model.
[So] Source:Brain;141(2):422-458, 2018 Feb 01.
[Is] ISSN:1460-2156
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood-brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood-brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath.awx350media15713427811001.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.1093/brain/awx350

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[PMID]: 28463821
[Au] Autor:Hoyt LR; Randall MJ; Ather JL; DePuccio DP; Landry CC; Qian X; Janssen-Heininger YM; van der Vliet A; Dixon AE; Amiel E; Poynter ME
[Ad] Address:Vermont Lung Center, University of Vermont, Burlington, VT 05405, USA; Division of Pulmonary Disease and Critical Care, Department of Medicine, University of Vermont, Burlington, VT 05405, USA.
[Ti] Title:Mitochondrial ROS induced by chronic ethanol exposure promote hyper-activation of the NLRP3 inflammasome.
[So] Source:Redox Biol;12:883-896, 2017 Aug.
[Is] ISSN:2213-2317
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Alcohol use disorders are common both in the United States and globally, and are associated with a variety of co-morbid, inflammation-linked diseases. The pathogenesis of many of these ailments are driven by the activation of the NLRP3 inflammasome, a multi-protein intracellular pattern recognition receptor complex that facilitates the cleavage and secretion of the pro-inflammatory cytokines IL-1ß and IL-18. We hypothesized that protracted exposure of leukocytes to ethanol would amplify inflammasome activation, which would help to implicate mechanisms involved in diseases associated with both alcoholism and aberrant NLRP3 inflammasome activation. Here we show that long-term ethanol exposure of human peripheral blood mononuclear cells and a mouse macrophage cell line (J774) amplifies IL-1ß secretion following stimulation with NLRP3 agonists, but not with AIM2 or NLRP1b agonists. The augmented NRLP3 activation was mediated by increases in iNOS expression and NO production, in conjunction with increases in mitochondrial membrane depolarization, oxygen consumption rate, and ROS generation in J774 cells chronically exposed to ethanol (CE cells), effects that could be inhibited by the iNOS inhibitor SEITU, the NO scavenger carboxy-PTIO, and the mitochondrial ROS scavenger MitoQ. Chronic ethanol exposure did not alter K efflux or Zn homeostasis in CE cells, although it did result in a lower intracellular concentration of NAD . Prolonged administration of acetaldehyde, the product of alcohol dehydrogenase (ADH) mediated metabolism of ethanol, mimicked chronic ethanol exposure, whereas ADH inhibition prevented ethanol-induced IL-1ß hypersecretion. Together, these results indicate that increases in iNOS and mitochondrial ROS production are critical for chronic ethanol-induced IL-1ß hypersecretion, and that protracted exposure to the products of ethanol metabolism are probable mediators of NLRP3 inflammasome hyperactivation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1705
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Process

  4 / 36610 MEDLINE  
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[PMID]: 29524138
[Au] Autor:Pyles B; Bailus BJ; O'Geen H; Segal DJ
[Ad] Address:Genome Center and Department of Biochemistry and Molecular Medicine, University of California, Davis, Davis, CA, USA.
[Ti] Title:Purified Protein Delivery to Activate an Epigenetically Silenced Allele in Mouse Brain.
[So] Source:Methods Mol Biol;1767:227-239, 2018.
[Is] ISSN:1940-6029
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The ability to activate or repress specific genes in the brain could have a tremendous impact for understanding and treating neurological disorders. Artificial transcription factors based on zinc finger, TALE, and CRISPR/Cas9 programmable DNA-binding platforms have been widely used to regulate the expression of specific genes in cultured cells, but their delivery into the brain represents a critical challenge to apply such tools in live animals. In previous work, we developed a purified, zinc finger-based artificial transcription factor that could be injected systemically, cross the blood-brain barrier, and alter expression of a specific gene in the brain of an adult mouse model of Angelman syndrome. Importantly, our mode of delivery produced widespread distribution throughout the brain. Here we describe our most current methods for the production and purification of the factor, dosage optimization, and use of live animal fluorescence imaging to visualize the kinetics of distribution.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:In-Data-Review
[do] DOI:10.1007/978-1-4939-7774-1_12

  5 / 36610 MEDLINE  
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[PMID]: 29522856
[Au] Autor:Brailoiu E; Barlow CL; Ramirez SH; Abood ME; Brailoiu GC
[Ad] Address:Center for Substance Abuse Research, Lewis Katz School of Medicine, Philadelphia, PA 19140, United states.
[Ti] Title:Effects of Platelet-Activating Factor on brain microvascular endothelial cells.
[So] Source:Neuroscience;, 2018 Mar 06.
[Is] ISSN:1873-7544
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Platelet-activating factor (PAF) is a potent phospholipid mediator that exerts various pathophysiological effects by interacting with a G protein-coupled receptor. PAF has been reported to increase the permeability of the blood-brain barrier (BBB) via incompletely characterized mechanisms. We investigated the effect of PAF on rat brain microvascular endothelial cells (RBMVEC), a critical component of the BBB. PAF produced a dose-dependent increase in cytosolic Ca concentration; the effect was prevented by the PAF receptor antagonist, WEB2086. The effect of PAF on cytosolic Ca was abolished in Ca -free saline or in the presence of L-type voltage-gated Ca channel inhibitor, nifedipine, indicating that Ca influx is critical for PAF-induced increase in cytosolic Ca . PAF produced RBMVEC depolarization; the effect was inhibited by WEB2086. In cells loaded with DAF-FM, a nitric oxide (NO)-sensitive fluorescent dye, PAF increased the NO level; the effect was prevented by WEB2086, nifedipine or by L-NAME, an inhibitor of NO synthase. Immunocytochemistry studies indicate that PAF reduced the immunostaining of ZO-1, a tight junction-associated protein, increased F-actin fibers, and produced intercellular gaps. PAF produced a decrease in RBMVEC monolayer electrical resistance assessed with Electric Cell-Substrate Impedance Sensing (ECIS), indicative of a disruption of endothelial barrier function. In vivo studies indicate that PAF increased the BBB permeability, assessed with sodium fluorescein and Evans Blue methods, via PAF receptor-dependent mechanisms, consequent to Ca influx and increased NO levels. Our studies reveal that PAF alters the BBB permeability by multiple mechanisms, which may be relevant for central nervous system (CNS) inflammatory disorders.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:Publisher

  6 / 36610 MEDLINE  
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[PMID]: 29446284
[Au] Autor:Kudaeva IV; Dyakovich OA; Beygel EA; Masnavieva LB; Naumova OV; Budarina LA
[Ti] Title:[Clinical, biochemical and allergological indices characterizing occupational diseases of the bronchial and pulmonary system in employees at aluminium production].
[So] Source:Gig Sanit;95(12):1142-5, 2016.
[Is] ISSN:0016-9900
[Cp] Country of publication:Russia (Federation)
[La] Language:rus
[Ab] Abstract:There are many harmful factors that possess a damaging impact on the body of employees at aluminum production. It leads to the development of bronchial asthma (BA), chronic nonobstructive bronchitis (CNB) and chronic obstructive pulmonary disease (COPD). The pathogenesis of these disorders, as well as sensitizing effect offluorine in the aluminum production is not fully understood. The purpose of this work was to study the characteristics of laboratory indices in patients with occupational diseases of the respiratory system. In workers of aluminum production with the diagnosis of occupational diseases of respiratory system (15 patients with a diagnosis of asthma, 30 CNB cases, 20 COPD patients) we evaluated the content of total protein, total cholesterol, high density lipoprotein cholesterol (HDLC), total calcium, phosphorus, ceruloplasmin, hematological indices and performed emigration of leukocytes braking test (TTEEL). Clinical and biochemical profile ofpersons with occupational asthma was characterized by a low level of total calcium and ceruloplasmin, a high concentration of phosphorus in the blood serum and inhibition of leukocyte emigration in the test with sodium fluoride. For aluminum production CNB workers characteristic active proatherogenic process was pronounced by a decrease in the HDLC level and an increase in atherogenic index; higher hematocrit value and concentration of erythrocytes, and more than 50% of cases of sensitization to the presence of sodium fluoride. COPD cases had occupational lower average concentration of hemoglobin in the erythrocyte, total protein in serum, as well as polymorphic variant response to sodium fluoride in the form of a depression and activation of leucocytes emigration.
[Mh] MeSH terms primary: Air Pollutants, Occupational
Aluminum
Asthma, Occupational
Chemical Industry
Pulmonary Disease, Chronic Obstructive
[Mh] MeSH terms secundary: Air Pollutants, Occupational/analysis
Air Pollutants, Occupational/toxicity
Aluminum/analysis
Aluminum/toxicity
Asthma, Occupational/blood
Asthma, Occupational/diagnosis
Asthma, Occupational/epidemiology
Biomarkers/analysis
Chemical Industry/methods
Chemical Industry/standards
Humans
Male
Middle Aged
Occupational Exposure/adverse effects
Occupational Exposure/analysis
Occupational Exposure/prevention & control
Occupational Health/statistics & numerical data
Pulmonary Disease, Chronic Obstructive/blood
Pulmonary Disease, Chronic Obstructive/diagnosis
Pulmonary Disease, Chronic Obstructive/epidemiology
Pulmonary Disease, Chronic Obstructive/etiology
Respiratory Hypersensitivity/blood
Respiratory Hypersensitivity/chemically induced
Respiratory Hypersensitivity/diagnosis
Siberia/epidemiology
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Air Pollutants, Occupational); 0 (Biomarkers); CPD4NFA903 (Aluminum)
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[Js] Journal subset:IM
[Da] Date of entry for processing:180216
[St] Status:MEDLINE

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[PMID]: 29507296
[Au] Autor:Hoseth EZ; Krull F; Dieset I; Mørch RH; Hope S; Gardsjord ES; Steen NE; Melle I; Brattbakk HR; Steen VM; Aukrust P; Djurovic S; Andreassen OA; Ueland T
[Ad] Address:NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
[Ti] Title:Exploring the Wnt signaling pathway in schizophrenia and bipolar disorder.
[So] Source:Transl Psychiatry;8(1):55, 2018 Mar 06.
[Is] ISSN:2158-3188
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:The Wnt signaling pathway plays a crucial role in neurodevelopment and in regulating the function and structure of the adult nervous system. Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders with evidence of subtle neurodevelopmental, structural and functional neuronal abnormalities. We aimed to elucidate the role of aberrant regulation of the Wnt system in these disorders by evaluating plasma levels of secreted Wnt modulators in patients (SCZ = 551 and BD = 246) and healthy controls (HCs = 639) using enzyme immune-assay. We also investigated the expression of 141 Wnt-related genes in whole blood in a subsample (SCZ = 338, BD = 241, and HCs = 263) using microarray analysis. Both SCZ and BD had dysregulated mRNA expression of Wnt-related genes favoring attenuated canonical (beta-catenin-dependent) signaling, and there were also indices of enhanced non-canonical Wnt signaling. In particular, FZD7, which may activate all Wnt pathways, but favors non-canonical signaling, and NFATc3, a downstream transcription factor and readout of the non-canonical Wnt/Ca pathway, were significantly increased in SCZ and BD (p < 3 × 10 ). Furthermore, patients had lower plasma levels of soluble dickkopf 1 and sclerostin (p < 0.01) compared with HC. Our findings suggest that SCZ and BD are characterized by abnormal Wnt gene expression and plasma protein levels, and we propose that drugs targeting the Wnt pathway may have a role in the treatment of severe mental disorders.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review
[do] DOI:10.1038/s41398-018-0102-1

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[PMID]: 29451141
[Au] Autor:Zhang R; Dong SY; Wang F; Ma C; Zhao XL; Zeng Q; Fei A
[Ad] Address:International Medical Center, Health Management Institute, Chinese PLA General Hospital, Beijing 100853; Department of Cardiology, Chinese Navy General Hospital, Beijing 100048, China.
[Ti] Title:Associations between Body Composition Indices and Metabolic Disorders in Chinese Adults: A Cross-Sectional Observational Study.
[So] Source:Chin Med J (Engl);131(4):379-388, 2018 Feb 20.
[Is] ISSN:0366-6999
[Cp] Country of publication:China
[La] Language:eng
[Ab] Abstract:Background: Obesity induces dyslipidemia, hypertension, glucose intolerance, and inflammatory state, which results in atherogenic processes, diabetes, and cardiovascular disease. We usually use body composition indices, such as body mass index (BMI), body fat percentage (BFP), waist circumference-height ratio (WHtR), and waist-hip ratio (WHR) to reflect the obesity. The aim of this large population-based cross-sectional study was to investigate the associations between body composition indices and metabolic parameters in Chinese adults. Methods: A total of 12,018 Chinese adults were included. Body composition indices, such as BMI, BFP, WHtR, and WHR, and metabolic parameters, such as systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), fasting blood glucose (FBG), 2 h postprandial blood glucose (2h PBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), insulin resistance index (HOMA-IR), high-sensitivity C-reactive protein (hs-CRP), and white blood cell count (WBC), were measured and analyzed. All analyses were stratified by gender. Results: All body composition indices and metabolic parameters except 2h PBG differed significantly between males and females (all P < 0.001). BMI was positively associated with SBP, DBP, LDL-C, TC, TG, FBG, 2h PBG, HbA1c, FINS, HOMA-IR, hs-CRP, and WBC, and inversely associated with HDL-C; similar relationships were identified between the metabolic parameters and BFP, WHtR, and WHR. In the multivariate analysis, the odds of impaired glucose regulation, dyslipidemia, insulin resistance, and increased hs-CRP were 1.36, 1.92, 3.44, and 1.27 times greater in the overweight group than those in the normal weight group, respectively, and 1.66, 3.26, 7.53, and 1.70 times greater in the obese group than those in the normal weight group, respectively. The odds of dyslipidemia and hs-CRP were 1.29 and 1.38 times greater in the BFP ≥28.0% group than in the BFP <28.0% group, respectively. The odds of dyslipidemia, HOMA-IR, and hs-CRP were 1.55, 1.26, and 1.48 times greater in the WHtR ≥0.96 group than in the WHtR <0.96 group, respectively. Among males, the odds of HOMA-IR were 1.46 times greater in the WHR ≥0.54 group than in the WHR <0.54 group. Similar results were observed in females. Conclusions: This study identified positive associations between all evaluated body composition indices and metabolic parameters in Chinese adults. Among the body composition indices, BMI predicted four of the five evaluated metabolic disorders in both gender groups.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Process
[do] DOI:10.4103/0366-6999.225059

  9 / 36610 MEDLINE  
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[PMID]: 28466272
[Au] Autor:Lin L; Wang Q; Qian K; Cao Z; Xiao J; Wang X; Li X; Yu Z
[Ad] Address:School of Pharmaceutical Sciences, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
[Ti] Title:bFGF Protects Against Oxygen Glucose Deprivation/Reoxygenation-Induced Endothelial Monolayer Permeability via S1PR1-Dependent Mechanisms.
[So] Source:Mol Neurobiol;55(4):3131-3142, 2018 Apr.
[Is] ISSN:1559-1182
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Blood-brain barrier (BBB) disruption is a common pathological feature of many neurological disorders including stroke and brain trauma, therefore is an important therapeutic target for treatment of these diseases. Basic fibroblast growth factor (bFGF) as a member of FGF superfamily plays critical roles in angiogenesis, neurogenesis, and neuron survival. We recently showed that recombinant bFGF protects against BBB disruption in traumatic brain injury in mice. In this study, we further investigated the mechanisms of recombinant bFGF in BBB protection by measuring the permeability of cultured endothelial cell monolayer induced by oxygen-glucose deprivation and reoxygenation (OGD/R). We found that recombinant bFGF significantly decreased OGD/R-induced permeability of primary human brain microvascular endothelial cell (HBMEC) monolayer and preserved OGD/R-induced decreases of trans-endothelial electrical resistance (TEER). Western blot and immunocytochemistry showed that bFGF significantly rescued OGD/R-induced downregulation of junction proteins ZO-1, occludin, and VE-cadherin. We further show that the BBB protective effect of bFGF is via FGF receptor 1 (FGFR1) activation as FGFR1 inhibitor can block this protection effect. Moreover, we revealed that the BBB protection effect of bFGF is at least partially through rescuing the OGD/R-induced downregulation of sphingosine-1-phosphate receptor 1 (S1PR1) protein, as S1PR1 inhibitor or SIPR1 small interfering RNA blocked the BBB protective effect of bFGF, whereas S1PR1 agonist alone has comparable BBB protection effect of bFGF. These findings will improve our understanding of the protective effect and mechanisms of bFGF on BBB and propose bFGF as a potential therapeutic agent against BBB damage in neurological disorders.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1705
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review
[do] DOI:10.1007/s12035-017-0544-0

  10 / 36610 MEDLINE  
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[PMID]: 28455701
[Au] Autor:da Silva Rocha-Lopes J; Machado RB; Suchecki D
[Ad] Address:Department of Psychobiology-Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Botucatu, 862, 1st floor, São Paulo, SP, 04023062, Brazil.
[Ti] Title:Chronic REM Sleep Restriction in Juvenile Male Rats Induces Anxiety-Like Behavior and Alters Monoamine Systems in the Amygdala and Hippocampus.
[So] Source:Mol Neurobiol;55(4):2884-2896, 2018 Apr.
[Is] ISSN:1559-1182
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Adolescence is marked by major physiological changes, including those in the sleep-wake cycle, such as phase delay, which may result in reduced sleep hours. Sleep restriction and/or deprivation in adult rats activate stress response and seem to be a risk factor for triggering emotional disorders. In the present study, we sought to evaluate the behavioral and neurobiological consequences of prolonged REM sleep restriction in juvenile male rats. Immediately after weaning, on postnatal day 21, three males from each litter were submitted to REM sleep deprivation and the other three animals were maintained in their home-cages. REM sleep restriction (REMSR) was accomplished by placing the animals in the modified multiple platform method for 18 h and 6 h in the home-cage, where they could sleep freely; the sleep restriction lasted 21 consecutive days, during which all animals were measured and weighed every 3 days. After the end of this period, all animals were allowed to sleep freely for 2 days, and then the behavioral tests were performed for evaluation of depressive and anxiety-like profiles (sucrose negative contrast test and elevated plus maze, EPM). Blood sampling was performed 5 min before and 30 and 60 min after the EPM for determination of corticosterone plasma levels. The adrenals were weighed and brains collected and dissected for monoamine levels and receptor protein expression. REMSR impaired the physical development of adolescents, persisting for a further week. Animals submitted to REMSR exhibited higher basal corticosterone levels and a greater anxiety index in the EPM, characteristic of an anxious profile. These animals also exhibited higher noradrenaline levels in the amygdala and ventral hippocampus, without any change in the expression of ß1-adrenergic receptors, as well as higher serotonin and reduced turnover in the dorsal hippocampus, with diminished expression of 5-HT1 . Finally, greater concentration of BDNF was observed in the dorsal hippocampus in chronically sleep-restricted animals. Chronic REMSR during puberty impaired physical development and induced anxiety-like behavior, attributed to increased noradrenaline and serotonin levels in the amygdala and hippocampus.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1704
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review
[do] DOI:10.1007/s12035-017-0541-3


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