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https://www.readbyqxmd.com/read/29691584/high-level-of-mn-in-brain-is-a-risk-for-alzheimer-disease
#1
Qin Yu, Yuan-Zhong Zhou
Alzheimer disease (AD) is a neurodegenerative disease. Manganese (Mn) is an essential trace element in the human body. It can enter the brain through the blood-brain barrier and blood-cerebrospinal fluid barrier. Excessive accumulation of Mn in the brain may disturb the homeostasis of the central nervous system (CNS) microenvironment and cause severe neuronal damage. The most recent data suggest that excessive Mn is associated with impaired learning and memory in animal models, and may lead to irreversible and progressive mild cognitive impairment and AD...
April 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/29691296/tryptophan-metabolism-contributes-to-radiation-induced-immune-checkpoint-reactivation-in-glioblastoma
#2
Pravin Kesarwani, Antony Prabhu, Shiva Kant, Praveen Kumar, Stewart F Graham, Katie L Buelow, George D Wilson, Christopher Ryan Miller, Prakash Chinnaiyan
PURPOSE: Immune checkpoint inhibitors designed to revert tumor-induced immune suppression have emerged as potent anti-cancer therapies. Tryptophan metabolism represents an immune checkpoint and targeting this pathway's rate limiting enzyme IDO1 is actively being investigated clinically. Here, we studied the intermediary metabolism of tryptophan metabolism in glioblastoma and evaluated the activity of the IDO1 inhibitor GDC-0919, both alone and in combination with radiation (RT).  Experimental Design: LC/GC-MS and expression profiling was performed for metabolomic and genomic analyses of patient-derived glioma...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29690789/protective-effects-of-ginsenoside-rb1-against-blood-brain-barrier-damage-induced-by-human-immunodeficiency-virus-1-tat-protein-and-methamphetamine-in-sprague-dawley-rats
#3
Juan Li, Bairui Zeng, Xiao Hu, Zhen Li, Dongxian Zhang, Genmeng Yang, Jiejie Dai, Xiaofeng Zeng
Although antiretroviral therapy has helped to improve the lives of individuals infected with human immunodeficiency virus 1 (HIV-1), these patients are often still afflicted with HIV-1-associated neurocognitive disorders, which can lead to neurocognitive impairment and even dementia, and continue to hamper their quality of life. Methamphetamine abuse in HIV-1 patients poses a potential risk for HIV-associated neurocognitive disorders, because methamphetamine and HIV-1 proteins such as transactivator of transcription can synergistically damage the blood-brain barrier (BBB)...
2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29689343/leveraging-genetics-to-enhance-the-efficacy-of-ptsd-pharmacotherapies
#4
REVIEW
Mark W Miller
Progress in PTSD pharmacotherapy has lagged far behind that of other major mental illnesses. Unfortunately, due to the enormous costs and lengthy process involved in bringing drugs to market, delivering new treatments to patients with PTSD in the near future will remain a challenge. However, by capitalizing on recent advances in the pharmacogenetics of antidepressants, precision psychiatry approaches can be leveraged to optimize the delivery of currently-available medications in a fraction of the time and cost required to develop novel therapeutics...
April 21, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29688865/brain-vascular-heterogeneity-implications-for-disease-pathogenesis-and-design-of-in-vitro-blood-brain-barrier-models
#5
REVIEW
Midrelle E Noumbissi, Bianca Galasso, Monique F Stins
The vertebrate blood-brain barrier (BBB) is composed of cerebral microvascular endothelial cells (CEC). The BBB acts as a semi-permeable cellular interface that tightly regulates bidirectional molecular transport between blood and the brain parenchyma in order to maintain cerebral homeostasis. The CEC phenotype is regulated by a variety of factors, including cells in its immediate environment and within functional neurovascular units. The cellular composition of the brain parenchyma surrounding the CEC varies between different brain regions; this difference is clearly visible in grey versus white matter...
April 23, 2018: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/29688408/spatiotemporal-distribution-of-fibrinogen-in-marmoset-and-human-inflammatory-demyelination
#6
Nathanael J Lee, Seung-Kwon Ha, Pascal Sati, Martina Absinta, Nicholas J Luciano, Jennifer A Lefeuvre, Matthew K Schindler, Emily C Leibovitch, Jae Kyu Ryu, Mark A Petersen, Afonso C Silva, Steven Jacobson, Katerina Akassoglou, Daniel S Reich
Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system. Although it has been extensively studied, the proximate trigger of the immune response remains uncertain. Experimental autoimmune encephalomyelitis in the common marmoset recapitulates many radiological and pathological features of focal multiple sclerosis lesions in the cerebral white matter, unlike traditional experimental autoimmune encephalomyelitis in rodents. This provides an opportunity to investigate how lesions form as well as the relative timing of factors involved in lesion pathogenesis, especially during early stages of the disease...
April 20, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29688337/stimulation-of-s1pr5-with-a-971432-a-selective-agonist-preserves-blood-brain-barrier-integrity-and-exerts-therapeutic-effect-in-an-animal-model-of-huntington-s-disease
#7
Alba Di Pardo, Salvatore Castaldo, Enrico Amico, Giuseppe Pepe, Federico Marracino, Luca Capocci, Alfredo Giovannelli, Michele Madonna, Jeroen van Bergeijk, Fabio Buttari, Elizabeth van der Kam, Vittorio Maglione
Huntington's disease (HD) is the most common neurodegenerative disorder for which no effective cure is yet available. Although several agents have been identified to provide benefits so far, the number of therapeutic options remains limited with only symptomatic treatment available. Over the past few years, we have demonstrated that sphingolipid-based approaches may open the door to new and more targeted treatments for the disease.In this study, we investigated the therapeutic potential of stimulating Sphingosine-1-phosphate (S1P) receptor 5 by the new selective agonist A-971432 (provided by AbbVie) in R6/2 mice, a widely-used HD animal model...
April 24, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29688083/localized-delivery-of-therapeutic-doxorubicin-dose-across-the-canine-blood-brain-barrier-with-hyperthermia-and-temperature-sensitive-liposomes
#8
Amy Lee Bredlau, Anjan Motamarry, Chao Chen, M A McCrackin, Kris Helke, Kent E Armeson, Katrina Bynum, Ann-Marie Broome, Dieter Haemmerich
Most drugs cannot penetrate the blood-brain barrier (BBB), greatly limiting the use of anti-cancer agents for brain cancer therapy. Temperature sensitive liposomes (TSL) are nanoparticles that rapidly release the contained drug in response to hyperthermia (>40 °C). Since hyperthermia also transiently opens the BBB, we hypothesized that localized hyperthermia can achieve drug delivery across the BBB when combined with TSL. TSL-encapsulated doxorubicin (TSL-Dox) was infused intravenously over 30 min at a dose of 0...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29687902/impact-of-metabolic-diseases-on-cerebral-circulation-structural-and-functional-consequences
#9
Maha Coucha, Mohammed Abdelsaid, Rebecca Ward, Yasir Abdul, Adviye Ergul
Metabolic diseases including obesity, insulin resistance, and diabetes have profound effects on cerebral circulation. These diseases not only affect the architecture of cerebral blood arteries causing adverse remodeling, pathological neovascularization, and vasoregression but also alter the physiology of blood vessels resulting in compromised myogenic reactivity, neurovascular uncoupling, and endothelial dysfunction. Coupled with the disruption of blood brain barrier (BBB) integrity, changes in blood flow and microbleeds into the brain rapidly occur...
March 25, 2018: Comprehensive Physiology
https://www.readbyqxmd.com/read/29687870/dl-3-n-butylphthalide-protects-the-blood-brain-barrier-of-cerebral-infarction-by-activating-the-nrf-2-ho-1-signaling-pathway-in-mice
#10
Y-J Zhao, Y Nai, Q-S Ma, D-J Song, Y-B Ma, L-H Zhang, L-X Mi
OBJECTIVE: The aim of this study was to explore whether Dl-3-n-butylphthalide (DBT) could protect blood-brain barrier (BBB) of mice with experimental cerebral infarction and the relevant mechanism. MATERIALS AND METHODS: Adult male CD-1 mice were selected as the study objects. The permanent middle cerebral artery occlusion (MCAO) model was prepared by Longa's modified suture-occluded method. The mice were randomly divided into 3 groups: the sham operation group (Sham group), the cerebral infarction model group (CI group) and the DBT (120 mg/kg) intervention group (DBT group)...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29687346/long-term-cognitive-outcomes-after-sepsis-a-translational-systematic-review
#11
REVIEW
Tatiana Barichello, Pavani Sayana, Vijayasree V Giridharan, Anithachristy S Arumanayagam, Boomadevi Narendran, Amanda Della Giustina, Fabricia Petronilho, João Quevedo, Felipe Dal-Pizzol
Sepsis is systemic inflammatory response syndrome with a life-threatening organ dysfunction that is caused by an unbalanced host immune response in an attempt to eliminate invasive microorganisms. We posed questions, "Does sepsis survivor patients have increased risk of neuropsychiatric manifestations?" and "What is the mechanism by which sepsis induces long-term neurological sequelae, particularly substantial cognitive function decline in survivor patients and in pre-clinical sepsis models?" The studies were identified by searching PubMed/MEDLINE (National Library of Medicine), PsycINFO, EMBASE (Ovid), LILACS (Latin American and Caribbean Health Sciences Literature), IBECS (Bibliographical Index in Spanish in Health Sciences), and Web of Science databases for peer-reviewed journals that were published until January 2018...
April 23, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29687323/investigation-of-cis-4-18-f-fluoro-d-proline-uptake-in-human-brain-tumors-after-multimodal-treatment
#12
Antoine Verger, Gabriele Stoffels, Norbert Galldiks, Philipp Lohmann, Antje Willuweit, Bernd Neumaier, Stefanie Geisler, Karl-Josef Langen
PURPOSE: Cis-4-[18 F]fluoro-D-proline (D-cis-[18 F]FPro) has been shown to pass the intact blood-brain barrier and to accumulate in areas of secondary neurodegeneration and necrosis in the rat brain while uptake in experimental brain tumors is low. This pilot study explores the uptake behavior of D-cis-[18 F]FPro in human brain tumors after multimodal treatment. PROCEDURES: In a prospective study, 27 patients with suspected recurrent brain tumor after treatment with surgery, radiotherapy, and/or chemotherapy (SRC) were investigated by dynamic positron emission tomography (PET) using D-cis-[18 F]FPro (22 high-grade gliomas, one unspecified glioma, and 4 metastases)...
April 23, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29686999/influence-of-drug-carrier-polymers-on-alpha-synucleinopathies-a-neglected-aspect-in-new-therapies-development
#13
C Tonda-Turo, M Herva, V Chiono, G Ciardelli, M G Spillantini
Current therapeutic strategies to treat neurodegenerative diseases, such as alpha-synucleinopathies, aim at enhancing the amount of drug reaching the brain. Methods proposed, such as intranasal administration, should be able to bypass the blood brain barrier (BBB) and even when directly intracerebrally injected they could require a carrier to enhance local release of drugs. We have investigated the effect of a model synthetic hydrogel to be used as drug carrier on the amount of alpha-synuclein aggregates in cells in culture...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29685987/characterization-of-a-two-component-system-transcriptional-regulator-ltdr-that-impacts-group-b-streptococcal-colonization-and-disease
#14
Liwen Deng, Rong Mu, Thomas A Weston, Brady L Spencer, Roxanne Liles, Kelly S Doran
Streptococcus agalactiae (Group B Streptococcus , GBS) is often a commensal bacterium that colonizes healthy adults asymptomatically and is a frequent inhabitant of the vaginal tract in women. However, in immune-compromised individuals, particularly the newborn, GBS may transition to an invasive pathogen and cause serious disease. Despite currently recommended intrapartum antibiotic prophylaxis for GBS-positive mothers, GBS remains a leading cause of neonatal septicemia and meningitis. To adapt to the various host environments encountered during its disease cycle, GBS possesses multiple two-component regulatory systems (TCS)...
April 23, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29685286/soluble-trem2-and-biomarkers-of-central-and-peripheral-inflammation-in-neurodegenerative-disease
#15
L M Bekris, M Khrestian, E Dyne, Y Shao, J A Pillai, S M Rao, S M Bemiller, B Lamb, H H Fernandez, J B Leverenz
Alzheimer's disease (AD) has been genetically and pathologically associated with neuroinflammation. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial receptor involved in innate immunity. TREM2 rare protein coding genetic variants have been linked to AD. A soluble TREM2 (sTREM2) cleavage product is elevated in AD. It is unclear whether there is a relationship between elevated sTREM2 and markers of inflammation. The hypothesis of this investigation was that central and peripheral inflammation play a role in sTREM2 levels in AD...
June 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29684592/cell-penetrating-peptides-for-sirna-delivery-to-glioblastomas
#16
Artita Srimanee, Maria Arvanitidou, Kumjee Kim, Mattias Hällbrink, Ülo Langel
Delivery of small interfering RNA (siRNA) to suppress glioblastoma growth is a hurdle due to the critical obstacles of the blood-brain barrier and the siRNA properties of such as high negative charges and instability in serum. Therefore, the passage of siRNA to targeted cells is limited. Several siRNA carriers have been constructed using cell-penetrating peptides (CPPs) since the CPPs have shown a high potential for oligonucleotide delivery into the cells. In this study, two CPPs, PepFect 14 (PF14) and the amphipathic peptide PepFect 28 (PF28), were modified with targeting peptides by covalent conjugation and non-covalent complex formation to improve glioma-targeted specificity and gene-silencing efficiency...
April 20, 2018: Peptides
https://www.readbyqxmd.com/read/29684590/a-synthetic-snake-venom-based-tripeptide-glu-val-trp-protects-pc12-cells-from-mpp-toxicity-by-activating-the-ngf-signaling-pathway
#17
Carolina P Bernardes, Neife A G Santos, Flavia M Sisti, Rafaela Scalco Ferreira, Norival A Santos-Filho, Adélia C O Cintra, Eduardo M Cilli, Suely V Sampaio, Antonio C Santos
Venom small peptides that target neurotrophin receptors might be beneficial in neurodegeneration, including Parkinsońs disease (PD). Their small size, ease of synthesis, structural stability and target selectivity make them important tools to overcome the limitations of endogenous neurotrophins as therapeutic agents. Additionally, they might be optimized to improve resistance to enzymatic degradation, bioavailability, potency and, mainly, lipophilicity, important to cross the blood brain barrier (BBB). Here, we evaluated the neuroprotective effects and mechanisms of the synthetic snake-venom-based peptide p-BTX-I (Glu-Val-Trp) in PC12 cells treated with MPP+ (1-methyl-4-phenylpyridinium), a dopaminergic neurotoxin that induces Parkinsonism in vivo...
April 20, 2018: Peptides
https://www.readbyqxmd.com/read/29684507/angiotensin-ii-type-1a-receptors-in-the-subfornical-organ-modulate-neuroinflammation-in-the-hypothalamic-paraventricular-nucleus-in-heart-failure-rats
#18
Yang Yu, Shun-Guang Wei, Robert M Weiss, Robert B Felder
Inflammation in the hypothalamic paraventricular nucleus (PVN) contributes to neurohumoral excitation and its adverse consequences in systolic heart failure (HF). The stimuli that trigger inflammation in the PVN in HF are not well understood. Angiotensin II (AngII) has pro-inflammatory effects, and circulating levels of AngII increase in HF. The subfornical organ (SFO), a circumventricular structure that lacks an effective blood-brain barrier and senses circulating AngII, contains PVN-projecting neurons. We hypothesized that activation of AngII type 1a receptors (AT1a R) in the SFO induces neuroinflammation downstream in the PVN...
April 20, 2018: Neuroscience
https://www.readbyqxmd.com/read/29684234/systemic-treatment-options-for-brain-metastases-from-non-small-cell-lung-cancer
#19
REVIEW
Ajaz Bulbul, Patrick M Forde, Ayesha Murtuza, Brian Woodward, Hannah Yang, Ingmar Bastian, Parissa K Ferguson, Fernando Lopez-Diaz, David S Ettinger, Hatim Husain
Brain metastases are common in patients with non-small-cell lung cancer (NSCLC). Because of associated poor prognosis and limited specific treatment options, there is a real need for the development of medical therapies and strategies for affected patients. Novel compounds for epidermal growth factor receptor-dependent and anaplastic lymphoma kinase-dependent lung cancer have demonstrated blood-brain barrier permeability and have led to important improvements in central nervous system outcomes. Studies of targeted therapies for oncogene-driven tumors and of immunotherapies in patients with brain metastases have shown promise and, allied with novel radiation techniques, are driving a rapid evolution in treatment and prognosis for NSCLC brain metastases...
April 15, 2018: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/29683403/paracellular-tightness-and-the-functional-expression-of-efflux-transporters-p-gp-and-bcrp-in-bend3-cells
#20
Shu Yang, Hong Jin, Zhigang Zhao
Objective The blood-brain barrier (BBB), regulating brain homeostasis and limiting the entry of most drugs, is characterized by intercellular tight junctions and the presence of transporters. In this study, the paracellular tightness and functional expression of efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) were evaluated in mouse brain immortalized cell line bEnd3 to prove it as a useful BBB-mimicking system for biological and pharmacological research. Methods The presence of P-gp, BCRP and tight junction proteins occludin, claudin-5 and ZO-1 were validated by RT-PCR and Western blot...
April 23, 2018: Neurological Research
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