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https://www.readbyqxmd.com/read/27911398/evaluation-of-bioenergetic-function-in-cerebral-vascular-endothelial-cells
#1
Stephanie L Rellick, Heng Hu, James W Simpkins, Xuefang Ren
The integrity of the blood-brain-barrier (BBB) is critical to prevent brain injury. Cerebral vascular endothelial (CVE) cells are one of the cell types that comprise the BBB; these cells have a very high-energy demand, which requires optimal mitochondrial function. In the case of disease or injury, the mitochondrial function in these cells can be altered, resulting in disease or the opening of the BBB. In this manuscript, we introduce a method to measure mitochondrial function in CVE cells by using whole, intact cells and a bioanalyzer...
November 19, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911307/a-high-cholesterol-diet-increases-27-hydroxycholesterol-and-modifies-estrogen-receptor-expression-and-neurodegeneration-in-rabbit-hippocampus
#2
Sylwia W Brooks, Ava C Dykes, Bernard G Schreurs
Hypercholesterolemia has been implicated in numerous health problems from cardiovascular disease to neurodegeneration. High serum cholesterol levels in midlife have been associated with an increased risk of developing Alzheimer's disease (AD) later in life which suggests that the pathways leading to AD pathology might be activated decades before the symptoms of the disease are detected. Cholesterol-fed animals, particularly cholesterol-fed rabbits, exhibit brain pathology similar to the changes found in brains of AD patients...
November 28, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27910074/evolutional-characterization-of-photochemically-induced-stroke-in-rats-a-multimodality-imaging-and-molecular-biological-study
#3
Nai-Wei Liu, Chien-Chih Ke, Yonghua Zhao, Yi-An Chen, Kim-Chuan Chan, David Tat-Wei Tan, Jhih-Shian Lee, You-Yin Chen, Tun-Wei Hsu, Ya-Ju Hsieh, Chi-Wei Chang, Bang-Hung Yang, Wen-Sheng Huang, Ren-Shyan Liu
Photochemically induced cerebral ischemia is an easy-manipulated, reproducible, relatively noninvasive, and lesion controllable model for translational study of ischemic stroke. In order to longitudinally investigate the characterization of the model, magnetic resonance imaging, (18)F-2-deoxy-glucose positron emission tomography, fluorescence, and bioluminescence imaging system were performed in correlation with triphenyl tetrazolium chloride (TTC), hematoxylin-eosin staining, and immunohistochemistry examinations of glial fibrillary acidic protein, CD68, NeuN, von willebrand factor, and α-smooth muscle actin in the infarct zone...
December 1, 2016: Translational Stroke Research
https://www.readbyqxmd.com/read/27909732/early-vegf-inhibition-attenuates-blood-brain-barrier-disruption-in-ischemic-rat-brains-by-regulating-the-expression-of-mmps
#4
Hai-Tao Zhang, Ping Zhang, Yi Gao, Chen-Long Li, Hong-Jun Wang, Ling-Chao Chen, Yan Feng, Rui-Yan Li, Yong-Li Li, Chuan-Lu Jiang
Vascular endothelial growth factor (VEGF) inhibition has been demonstrated to be an effective strategy in preserving the integrity of the blood-brain barrier (BBB) in patients with acute ischemic stroke. Loss of the BBB is the key event associated with morbidity and mortality in these patients. However, the underlying mechanisms remain poorly understood. In the present study, the effects of VEGF inhibition and the possible mechanism that underlies acute cerebral ischemia in rats was investigated. Following the induction of transient middle cerebral artery occlusion for a 90‑min period, either an anti‑VEGF neutralizing antibody (RB‑222; 5 or 10 µg), or IgG (control), was administered by intracerebroventricular injection at 1 h following reperfusion...
November 29, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27909202/prediction-of-blood-brain-barrier-disruption-and-intracerebral-hemorrhagic-infarction-using-arterial-spin-labeling-magnetic-resonance-imaging
#5
Takeya Niibo, Hajime Ohta, Shirou Miyata, Ichiro Ikushima, Kazuchika Yonenaga, Hideo Takeshima
BACKGROUND AND PURPOSE: Arterial spin-labeling magnetic resonance imaging is sensitive for detecting hyperemic lesions (HLs) in patients with acute ischemic stroke. We evaluated whether HLs could predict blood-brain barrier (BBB) disruption and hemorrhagic transformation (HT) in acute ischemic stroke patients. METHODS: In a retrospective study, arterial spin-labeling was performed within 6 hours of symptom onset before revascularization treatment in 25 patients with anterior circulation large vessel occlusion on baseline magnetic resonance angiography...
December 1, 2016: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/27908752/n-propargylpiperidines-with-naphthalene-2-carboxamide-or-naphthalene-2-sulfonamide-moieties-potential-multifunctional-anti-alzheimer-s-agents
#6
Urban Košak, Damijan Knez, Nicolas Coquelle, Boris Brus, Anja Pišlar, Florian Nachon, Xavier Brazzolotto, Janko Kos, Jacques-Philippe Colletier, Stanislav Gobec
In the brains of patients with Alzheimer's disease, the enzymatic activities of butyrylcholinesterase (BChE) and monoamine oxidase B (MAO-B) are increased. While BChE is a viable therapeutic target for alleviation of symptoms caused by cholinergic hypofunction, MAO-B is a potential therapeutic target for prevention of neurodegeneration in Alzheimer's disease. Starting with piperidine-based selective human (h)BChE inhibitors and propargylamine-based MAO inhibitors, we have designed, synthesized and biochemically evaluated a series of N-propargylpiperidines...
November 19, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27907954/today-s-approach-to-treating-brain-swelling-in-the-neuro-intensive-care-unit
#7
Shreyansh Shah, W Taylor Kimberly
Brain swelling is an urgent clinical problem that frequently accompanies ischemic stroke, brain hemorrhage, and traumatic brain injury; it increases morbidity and mortality associated with them. It occurs due to failure of membrane transporters and leakage of the blood-brain barrier (BBB), resulting in combination of cytotoxic, ionic, and vasogenic edema. Currently, decompressive craniectomy and osmotherapy are the mainstays of management, but these therapies do not halt the underlying molecular cascade leading to brain swelling...
December 2016: Seminars in Neurology
https://www.readbyqxmd.com/read/27907158/effects-of-exposure-to-blast-overpressure-on-intracranial-pressure-and-blood-brain-barrier-permeability-in-a-rat-model
#8
Usmah Kawoos, Ming Gu, Jason Lankasky, Richard M McCarron, Mikulas Chavko
Exposure to blast overpressure (BOP) activates a cascade of pathological processes including changes in intracranial pressure (ICP) and blood-brain barrier (BBB) permeability resulting in traumatic brain injury (TBI). In this study the effect of single and multiple exposures at two intensities of BOP on changes in ICP and BBB permeability in Sprague-Dawley rats was evaluated. Animals were exposed to a single or three repetitive (separated by 0.5 h) BOPs at 72 kPa or 110 kPa. ICP was monitored continuously via telemetry for 6 days after exposure to BOP...
2016: PloS One
https://www.readbyqxmd.com/read/27907083/effects-of-acute-systemic-hypoxia-and-hypercapnia-on-brain-damage-in-a-rat-model-of-hypoxia-ischemia
#9
Wanchao Yang, Xuezhong Zhang, Nan Wang, Jing Tan, Xianhai Fang, Qi Wang, Tao Tao, Wenzhi Li
Therapeutic hypercapnia has the potential for neuroprotection after global cerebral ischemia. Here we further investigated the effects of different degrees of acute systemic hypoxia in combination with hypercapnia on brain damage in a rat model of hypoxia and ischemia. Adult wistar rats underwent unilateral common carotid artery (CCA) ligation for 60 min followed by ventilation with normoxic or systemic hypoxic gas containing 11%O2,13%O2,15%O2 and 18%O2 (targeted to PaO2 30-39 mmHg, 40-49 mmHg, 50-59 mmHg, and 60-69 mmHg, respectively) or systemic hypoxic gas containing 8% carbon dioxide (targeted to PaCO2 60-80 mmHg) for 180 min...
2016: PloS One
https://www.readbyqxmd.com/read/27906602/meta-analysis-of-pre-clinical-trials-of-therapeutic-hypothermia-for-intracerebral-hemorrhage
#10
Kara R Melmed, Patrick D Lyden
Therapeutic hypothermia (TH) is a potent neuroprotectant for experimental ischemic stroke, but studies of TH for intracerebral hemorrhage (ICH) are emerging. We systematically reviewed the experimental literature to assess TH efficacy for ICH. We found 18 suitable papers; quality scores were moderately good. Compared with normothermia, TH reduced measures of edema (mean effect size (95% CI) -1.6873 (-2.3640, -1.0106), p < 0.0001) or blood-brain barrier leakage (p < 0.0001) and improved behavioral outcomes (p < 0...
December 1, 2016: Therapeutic Hypothermia and Temperature Management
https://www.readbyqxmd.com/read/27906525/the-clinical-utility-of-qsm-disease-diagnosis-medical-management-and-surgical-planning
#11
REVIEW
Sarah Eskreis-Winkler, Yan Zhang, Jingwei Zhang, Zhe Liu, Alexey Dimov, Ajay Gupta, Yi Wang
Quantitative susceptibility mapping (QSM) is an MR technique that depicts and quantifies magnetic susceptibility sources. Mapping iron, the dominant susceptibility source in the brain, has many important clinical applications. Herein, we review QSM applications in the diagnosis, medical management, and surgical treatment of disease. To assist in early disease diagnosis, QSM can identify elevated iron levels in the motor cortex of amyotrophic lateral sclerosis patients, in the substantia nigra of Parkinson's disease (PD) patients, in the globus pallidus, putamen, and caudate of Huntington's disease patients, and in the basal ganglia of Wilson's disease patients...
December 1, 2016: NMR in Biomedicine
https://www.readbyqxmd.com/read/27905989/the-histone-deacetylase-inhibitor-sodium-butyrate-exhibits-neuroprotective-effects-for-ischemic-stroke-in-middle-aged-female-rats
#12
Min Jung Park, Farida Sohrabji
BACKGROUND: Sodium butyrate (NaB) is a histone deacetylase (HDAC) inhibitor exhibiting anti-inflammatory and neuroprotective effects in a rat ischemic model of stroke as well as a myocardial ischemia model. Although clinical evidence shows that older women are at higher risk for stroke occurrence and greater stroke severity, no studies have evaluated the effectiveness of NaB either in females or in older animals. METHODS: To determine the effects of NaB on stroke in older females, acyclic middle-aged Sprague-Dawley female rats (9-11 months old, constant diestrus) were subject to middle cerebral artery occlusion (MCAo) by intracerebral injection of recombinant endothelin-1...
December 1, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27903802/a-protective-role-for-il-1-signaling-during-mouse-adenovirus-type-1-induced-encephalitis
#13
Luiza A Castro-Jorge, Carla Pretto, Asa Smith, Oded Foreman, Kelly E Carnahan, Katherine R Spindler
: IL-1β, an inflammatory cytokine and IL-1 receptor ligand, has diverse activities in the brain. We examined whether IL-1 signaling contributes to the encephalitis observed in mouse adenovirus type 1 (MAV-1) infection, using mice lacking the IL-1 receptor, Il1r1(-/-) Il1r1(-/-) mice had lower survival, higher disruption of the blood-brain barrier (BBB), higher brain viral loads, and higher brain inflammatory cytokines and chemokines than control C57BL/6 mice. We also examined infections of mice defective in IL-1β production (Pycard(-/-)mice) and mice defective in trafficking of TLRs to the endosome (Unc93b1(-/-) mice)...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27903281/improving-the-clinical-management-of-traumatic-brain-injury-through-the-pharmacokinetic-modeling-of-peripheral-blood-biomarkers
#14
Aaron Dadas, Jolewis Washington, Nicola Marchi, Damir Janigro
BACKGROUND: Blood biomarkers of neurovascular damage are used clinically to diagnose the presence severity or absence of neurological diseases, but data interpretation is confounded by a limited understanding of their dependence on variables other than the disease condition itself. These include half-life in blood, molecular weight, and marker-specific biophysical properties, as well as the effects of glomerular filtration, age, gender, and ethnicity. To study these factors, and to provide a method for markers' analyses, we developed a kinetic model that allows the integrated interpretation of these properties...
November 30, 2016: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/27903215/identification-of-novel-agents-for-the-treatment-of-brain-metastases-of-breast-cancer
#15
Vinay Kumar Venishetty, Werner J Geldenhuys, Tori B Terell-Hall, Jessica I G Griffith, Gregory R Sondag, Fayez F Safadi, Paul R Lockman
BACKGROUND: Brain cancer from metastasized breast cancer has a high mortality rate in women. The treatment of lesions is hampered in large part by the blood-brain barrier (BBB), which prevents adequate distribution of anti-cancer compounds to brain metastases. METHOD: In this study we used a novel screening method to identify candidate molecules that are well-suited to utilizing the BBB choline transporter for distribution into the brain parenchyma. RESULTS: From our screen we identified two compounds, Ch-1 and Ch-2 that were able to reduce the brain tumor burden in a murine mouse model of brain metastasis of breast cancer...
November 21, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27902880/monoamine-oxidase-inhibitory-activity-methyl-versus-chlorochalcone-derivatives
#16
Bijo Mathew, Gülberk Uçar, Githa Elizabeth Mathew, Sincy Mathew, Praseedha Kalatharakkal Purapurath, Fasil Moolayil, Smrithy Mohan, Sheeba Varghese Gupta
Numerous studies have shown that chalcones are promising scaffolds for the development of new monoamine oxidase-B (MAO-B) inhibitors. As a continuation of our ongoing research into the development of reversible human MAO-B (hMAO-B) inhibitors, two series of twenty chalcones containing electron-donating and electron-withdrawing substituents were synthesized. All compounds were found to be competitive, selective, and reversible inhibitors of hMAO-B except (2E)-1-(4-methylphenyl)-3-(4-nitrophenyl)prop-2-en-1-one (P7) and (2E)-1-(4-chlorophenyl)-3-(4-nitrophenyl)prop-2-en-1-one (P17), which were found to be selective inhibitors of hMAO-A...
November 30, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27902858/reliable-estimation-of-microvascular-flow-patterns-in-patients-with-disrupted-blood-brain-barrier-using-dynamic-susceptibility-contrast-mri
#17
Mikkel Bo Hansen, Anna Tietze, Jayashree Kalpathy-Cramer, Elizabeth R Gerstner, Tracy T Batchelor, Leif Østergaard, Kim Mouridsen
PURPOSE: To present and quantify the performance of a method to compute tissue hemodynamic parameters from dynamic susceptibility contrast (DSC) MRI data in brain tissue with possible nonintact blood-brain barrier. THEORY AND MATERIALS AND METHODS: We propose a Bayesian scheme to obtain perfusion metrics, including capillary transit-time heterogeneity (CTH), from DSC-MRI data in the presence of contrast agent extravasation. Initial performance assessment is performed through simulations...
November 30, 2016: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/27902458/dna-sequences-within-glioma-derived-extracellular-vesicles-can-cross-the-intact-blood-brain-barrier-and-be-detected-in-peripheral-blood-of-patients
#18
Noemí García-Romero, Josefa Carrión-Navarro, Susana Esteban-Rubio, Elisa Lázaro-Ibáñez, María Peris-Celda, Marta M Alonso, Juan Guzmán-De-Villoria, Carlos Fernández-Carballal, Ana Ortiz de Mendivil, Sara García-Duque, Carmen Escobedo-Lucea, Ricardo Prat-Acín, Cristóbal Belda-Iniesta, Angel Ayuso-Sacido
Tumor-cell-secreted extracellular vesicles (EVs) can cross the disrupted blood-brain barrier (BBB) into the bloodstream. However, in certain gliomas, the BBB remains intact, which might limit EVs release. To evaluate the ability of tumor-derived EVs to cross the BBB, we used an orthotopic xenotransplant mouse model of human glioma-cancer stem cells featuring an intact BBB. We demonstrated that all types of tumor cells-derived EVs-apoptotic bodies, shedding microvesicles and exosomes-cross the intact BBB and can be detected in the peripheral blood, which provides a minimally invasive method for their detection compared to liquid biopsies obtained from cerebrospinal fluid (CSF)...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901023/rhein-and-rhubarb-similarly-protect-the-blood-brain-barrier-after-experimental-traumatic-brain-injury-via-gp91-phox-subunit-of-nadph-oxidase-ros-erk-mmp-9-signaling-pathway
#19
Yang Wang, Xuegong Fan, Tao Tang, Rong Fan, Chunhu Zhang, Zebing Huang, Weijun Peng, Pingping Gan, Xingui Xiong, Wei Huang, Xi Huang
Oxidative stress chiefly contributes to the disruption of the BBB following traumatic brain injury (TBI). The Chinese herbal medicine rhubarb is a promising antioxidant in treating TBI. Here we performed in vivo and in vitro experiments to determine whether rhubarb and its absorbed bioactive compound protected the BBB after TBI by increasing ZO-1 expression through inhibition of gp91(phox) subunit of NADPH oxidase/ROS/ERK/MMP-9 pathway. Rats were subjected to the controlled cortical impact (CCI) model, and primary rat cortical astrocytes were exposed to scratch-wound model...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899068/title-role-of-matrix-metalloproteinase-9-in-progression-of-tuberculous-meningitis-a-pilot-study-in-patients-at-different-stages-of-the-disease
#20
S Majeed, P Singh, N Sharma, S Sharma
BACKGROUND: TBM (Tuberculous meningitis) is severe form of tuberculosis causing death of one third of the affected individuals or leaving two-third of the survivors disabled. MMP-9 (Matrix metalloproteinase-9) is produced by the central nervous system in a variety of inflammatory conditions and has a role in the breakdown of extracellular matrix and blood-brain barrier. METHODS: In this study, the levels of MMP-9 and its inhibitor, TIMP-1 (tissue inhibitor of metalloproteinases-1), were screened using zymography and reverse zymography in cerebrospinal fluid and serum of tuberculous meningitis patients at different stages of the disease...
November 29, 2016: BMC Infectious Diseases
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