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https://www.readbyqxmd.com/read/28632387/poly-trehalose-nanoparticle-prevents-amyloid-aggregation-and-suppress-polyglutamine-aggregation-in-huntington-s-disease-model-mouse
#1
Koushik Debnath, Nibedita Pradhan, Brijesh Kumar Singh, Nihar R Jana, Nikhil R Jana
Prevention and therapeutic strategy of various neurodegenerative disease focus on inhibiting protein fibrillation, clearing of aggregated protein plaques from brain and lowering of protein aggregate-induced toxicity. We have designed poly(trehalose) nanoparticle that can inhibit amyloid/polyglutamine aggregation under extra-/intra-cellular condition, reduce such aggregation-derived cytotoxicity and prevents polyglutamine aggregation in Huntington's disease (HD) model mouse brain. Nanoparticle has 20-30 nm hydrodynamic size, composed of 6 nm iron oxide core and zwitterionic polymer shell with covalently linked trehalose of ~5-12 wt %...
June 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28615985/treatment-of-movement-disorders-with-focused-ultrasound
#2
REVIEW
Paul S Fishman, Victor Frenkel
Although the use of ultrasound as a potential therapeutic modality in the brain has been under study for several decades, relatively few neuroscientists or neurologists are familiar with this technology. Stereotactic brain lesioning had been widely used as a treatment for medically refractory patients with essential tremor (ET), Parkinson disease (PD), and dystonia but has been largely replaced by deep brain stimulation (DBS) surgery, with advantages both in safety and efficacy. However, DBS is associated with complications including intracerebral hemorrhage, infection, and hardware malfunction...
2017: Journal of Central Nervous System Disease
https://www.readbyqxmd.com/read/28604104/intranasal-delivery-of-quercetin-loaded-mucoadhesive-nanoemulsion-for-treatment-of-cerebral-ischaemia
#3
Niyaz Ahmad, Rizwan Ahmad, Atta Abbas Naqvi, Md Aftab Alam, Mohammad Ashafaq, Rehan Abdur Rub, Farhan Jalees Ahmad
BACKGROUND: Quercetin (QUR), as an antioxidant flavonoid, exhibits potential role in the amelioration of cerebral ischaemia; however, poor solubility as well as oral absorption results low serum and tissue levels for this drug. PURPOSE OF THE STUDY: To enhance bioavailability, this study aims to prepare QUR nanoemulsions and administer via non-invasive nasal route in order to evaluate the drug targeting in brain. METHODS: Quercetin mucoadhesive nanoemulsion (QMNE) was prepared (ionic gelation method) and optimized using various parameters, that is, particle size, entrapment efficiency, zeta potential and ex vivo permeation study...
June 12, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28598844/combustion-derived-nanoparticles-in-key-brain-target-cells-and-organelles-in-young-urbanites-culprit-hidden-in-plain-sight-in-alzheimer-s-disease-development
#4
Angélica González-Maciel, Rafael Reynoso-Robles, Ricardo Torres-Jardón, Partha S Mukherjee, Lilian Calderón-Garcidueñas
Millions of children and young adults are exposed to fine particulate matter (PM2.5) and ozone, associated with Alzheimer's disease (AD) risk. Mexico City (MC) children exhibit systemic and brain inflammation, low cerebrospinal fluid (CSF) Aβ1-42, breakdown of nasal, olfactory, alveolar-capillary, duodenal, and blood-brain barriers, volumetric and metabolic brain changes, attention and short-term memory deficits, and hallmarks of AD and Parkinson's disease. Airborne iron-rich strongly magnetic combustion-derived nanoparticles (CDNPs) are present in young urbanites' brains...
June 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28592843/pluronic-f127-and-d-%C3%AE-tocopheryl-polyethylene-glycol-succinate-tpgs-mixed-micelles-for-targeting-drug-delivery-across-the-blood-brain-barrier
#5
Xin Meng, Jiansheng Liu, Xiangrong Yu, Jiajia Li, Xiaotong Lu, Teng Shen
A novel polymeric mixed micelle composed of Pluronic F127 and D-α-tocopheryl polyethylene glycol succinate (TPGS) was developed to improve the delivery of fluorescent dyes and protein across the blood brain barrier (BBB). Rhodamine 123 (Rho123) and DiR loaded mixed micelles, composed of Pluronic F127 and TPGS with proportion of 4:1 (FT), were prepared by thin-film hydration, and β-galactosidase (β-Gal) loaded FT mixed micelles were prepared by self-assembly. The brain-targeted capability of FT mixed micelles were evaluated both in vitro and in vivo...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28574732/in-vitro-and-in-vivo-evaluation-of-cubosomal-in-situ-nasal-gel-containing-resveratrol-for-brain-targeting
#6
Mayuri Ahirrao, Shilpa Shrotriya
The aim of this study was to enhance the delivery of resveratrol to the brain through the transnasal route by cubosomes. Cubosomes were prepared using glycerol monooleate and Lutrol F127 by probe sonication method. A 3(2) full factorial design was used for optimization of cubosomes and batch containing 4% w/v glycerol monooleate and 1.5% w/v of Lutrol F 127 was optimized. The selected cubosomal batch was cubical in shape, having mean particle size 161.5±0.12 nm. Entrapment efficiency was found to be 83.08% with zeta potential of - 20...
June 2, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28570514/single-cell-rna-seq-of-defined-subsets-of-retinal-ganglion-cells
#7
Lauren A Laboissonniere, Takuma Sonoda, Seul Ki Lee, Jeffrey M Trimarchi, Tiffany M Schmidt
The discovery of cell type-specific markers can provide insight into cellular function and the origins of cellular heterogeneity. With a recent push for the improved understanding of neuronal diversity, it is important to identify genes whose expression defines various subpopulations of cells. The retina serves as an excellent model for the study of central nervous system diversity, as it is composed of multiple major cell types. The study of each major class of cells has yielded genetic markers that facilitate the identification of these populations...
May 22, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28566948/clinical-and-autoimmune-features-of-a-patient-with-autism-spectrum-disorder-seropositive-for-anti-nmda-receptor-autoantibody
#8
Hélène Gréa, Isabelle Scheid, Alexandru Gaman, Véronique Rogemond, Sandy Gillet, Jérôme Honnorat, Federico Bolognani, Christian Czech, Céline Bouquet, Elie Toledano, Manuel Bouvard, Richard Delorme, Laurent Groc, Marion Leboyer
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by dysfunctions in social interactions resulting from a complex interplay between immunogenetic and environmental risk factors. Autoimmunity has been proposed as a major etiological component of ASD. Whether specific autoantibodies directed against brain targets are involved in ASD remains an open question. Here, we identified within a cohort an ASD patient with multiple circulating autoantibodies, including the well-characterized one against glutamate NMDA receptor (NMDAR-Ab)...
March 2017: Dialogues in Clinical Neuroscience
https://www.readbyqxmd.com/read/28557603/genome-wide-methyl-seq-analysis-of-blood-brain-targets-of-glucocorticoid-exposure
#9
Fayaz Seifuddin, Gary Wand, Olivia Cox, Mehdi Pirooznia, Laura Moody, Xiaoju Yang, Jonathan Tai, Gretha Boersma, Kellie Tamashiro, Peter Zandi, Richard Lee
Chronic exposure to glucocorticoids (GCs) can lead to psychiatric complications through epigenetic mechanisms such as DNA methylation (DNAm). We sought to determine whether epigenetic changes in a peripheral tissue can serve as a surrogate for those in a relatively inaccessible tissue such as the brain. DNA extracted from the hippocampus and blood of mice treated with GCs or vehicle solution was assayed using a genome-wide DNAm platform (Methyl-Seq) to identify differentially methylated regions (DMRs) induced by GC treatment...
May 30, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28549949/recent-advancements-in-liposomes-targeting-strategies-to-cross-blood-brain-barrier-bbb-for-the-treatment-of-alzheimer-s-disease
#10
REVIEW
Mukta Agrawal, Ajazuddin, Dulal K Tripathi, Swarnlata Saraf, Shailendra Saraf, Sophia G Antimisiaris, Spyridon Mourtas, Margareta Hammarlund-Udenaes, Amit Alexander
In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli...
May 24, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28532338/design-of-amphiphilic-pcl-peg-pcl-block-copolymers-as-vehicles-of-ginkgolide-b-and-their-brain-targeting-studies
#11
Xi-Qing Yan, Yong-Li Shi, Qing-Feng Jiang, Guan-Fang Ping, Zhi-Jian Deng
The amphiphilic PEG-b-PCL block copolymers were synthesized by ring-opening polymerization. The specific and selective antagonists of platelet activating factor, Ginkgolide B (GB), was successfully encapsulated in the synthesized PEG-PCL nanoparticles (NPs) with high Encapsulation Efficiency and Drug Loading. The synthesis of different PEG-PCL copolymers were confirmed with FTIR and (1)H NMR spectra. The morphology and particles size distribution of cargo-free PEG-PCL NPs were studied by transmission electron microscope (TEM) analysis and Malvern laser particle analyzer...
May 28, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28504886/nanoparticle-delivered-2-pam-for-rat-brain-protection-against-paraoxon-central-toxicity
#12
Tatiana N Pashirova, Irina V Zueva, Konstantin A Petrov, Vasily M Babaev, Svetlana S Lukashenko, Ildar Kh Rizvanov, Eliana B Souto, Evgeny E Nikolsky, Lucia Ya Zakharova, Patrick Masson, Oleg G Sinyashin
Solid lipid nanoparticles (SLNs) are among the most promising nanocarriers to target the blood-brain barrier (BBB) for drug delivery to the central nervous system (CNS). Encapsulation of the acetylcholinesterase reactivator, pralidoxime chloride (2-PAM), in SLNs appears to be a suitable strategy for protection against poisoning by organophosphorus agents (OPs) and postexposure treatment. 2-PAM-loaded SLNs were developed for brain targeting and delivery via intravenous (iv) administration. 2-PAM-SLNs displayed a high 2-PAM encapsulation efficiency (∼90%) and loading capacity (maximum 30...
May 15, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28502631/a-brain-targeted-ampakine-compound-protects-against-opioid-induced-respiratory-depression
#13
Wei Dai, Dian Xiao, Xiang Gao, Xin-Bo Zhou, Tong-Yu Fang, Zheng Yong, Rui-Bin Su
The use of opioid drugs for pain relief can induce life-threatening respiratory depression. Although naloxone effectively counteracts opioid-induced respiratory depression, it diminishes the efficacy of analgesia. Our studies indicate that ampakines, in particular, a brain-targeted compound XD-8-17C, are able to reverse respiratory depression without affecting analgesia at relatively low doses. Mice and rats were subcutaneously or intravenously injected with the opioid agonist TH-030418 to induce moderate or severe respiratory depression...
May 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28498148/striatal-activity-is-modulated-by-target-probability
#14
Nicholas Hon
Target probability has well-known neural effects. In the brain, target probability is known to affect frontal activity, with lower probability targets producing more prefrontal activation than those that occur with higher probability. Although the effect of target probability on cortical activity is well specified, its effect on subcortical structures such as the striatum is less well understood. Here, I examined this issue and found that the striatum was highly responsive to target probability. This is consistent with its hypothesized role in the gating of salient information into higher-order task representations...
June 14, 2017: Neuroreport
https://www.readbyqxmd.com/read/28494740/nucleic-acids-based-nanotherapeutics-crossing-the-blood-brain-barrier
#15
Noha Nafee, Noha Gouda
The restless endeavors revealing the molecular pathways underlying many neurodegenerative diseases and brain tumors have paved the way for the introduction of the selective exogenous gene-based therapeutics. The implicated active biomolecules encompass mainly negatively-charged nucleic acids ranging from DNA, mRNA, non-coding RNAs (small-interfering RNA, siRNA, and microRNA, miRNA), to antisense oligonucleotides. They selectively interfere with the genes translational and/or transcriptional processes. Although many reviews previously addressed brain targeting, a thorough correlation between the molecular properties of these biomacromolecules, the nature of blood brain barrier (BBB) in the accompanying pathological condition, the intracellular targets, as well as the design of the delivery system which will transport the bioactive cargo to the target cells attempting efficient delivery to the active sites in the brain will be appraised...
May 10, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28476614/a-strategy-for-bypassing-the-blood-brain-barrier-facial-intradermal-brain-targeted-delivery-via-the-trigeminal-nerve
#16
Xi-Chong Yu, Jing-Jing Yang, Bing-Hui Jin, He-Lin Xu, Hong-Yu Zhang, Jian Xiao, Cui-Tao Lu, Ying-Zheng Zhao, Wei Yang
Although intranasal delivery bypasses the blood-brain barrier (BBB), the anatomical location of the olfactory mucosa and respiratory airflow interference lead to less brain-targeted drug delivery. In addition to intranasal delivery, evidence indicates that facial intradermal injection might be a novel strategy for bypassing the BBB via the trigeminal nerve (TN). The hypothesis was verified by pharmacokinetic evaluation, nasal injury, lymphatic vessels inhibition and immunohistochemistry. Intradermal injection into the rat mystacial pad (i...
May 2, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28436502/arsenolipids-exert-less-toxicity-in-a-human-neuron-astrocyte-co-culture-as-compared-to-the-respective-monocultures
#17
B Witt, J Bornhorst, H Mitze, F Ebert, S Meyer, K A Francesconi, T Schwerdtle
Arsenic-containing hydrocarbons (AsHCs), natural products found in seafood, have recently been shown to exert toxic effects in human neurons. In this study we assessed the toxicity of three AsHCs in cultured human astrocytes. Due to the high cellular accessibility and substantial toxicity observed astrocytes were identified as further potential brain target cells for arsenolipids. Thereby, the AsHCs exerted a 5-19-fold higher cytotoxicity in astrocytes as compared to arsenite. Next we compared the toxicity of the arsenicals in a co-culture model of the respective human astrocytes and neurons...
May 24, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28415883/electrosteric-stealth-rivastigmine-loaded-liposomes-for-brain-targeting-preparation-characterization-ex-vivo-bio-distribution-and-in-vivo-pharmacokinetic-studies
#18
Sara Nageeb El-Helaly, Ahmed Abd Elbary, Mohamed A Kassem, Mohamed A El-Nabarawi
Being one of the highly effective drugs in treatment of Alzheimer's disease, Rivastigmine brain targeting is highly demandable, therefore liposomal dispersion of Rivastigmine was prepared containing 2 mol% PEG-DSPE added to Lecithin, Didecyldimethyl ammonium bromide (DDAB), Tween 80 in 1:0.02:0.25 molar ratio. A major challenge during the preparation of liposomes is maintaining a stable formulation, therefore the aim of our study was to increase liposomal stability by addition of DDAB to give an electrostatic stability and PEG-DSPE to increase stability by steric hindrance, yielding what we called an electrosteric stealth (ESS) liposomes...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28408348/design-and-in-vivo-evaluation-of-solid-lipid-nanoparticulate-systems-of-olanzapine-for-acute-phase-schizophrenia-treatment-investigations-on-antipsychotic-potential-and-adverse-effects
#19
Emil Joseph, Satish Reddi, Vibhu Rinwa, Garima Balwani, Ranendra Saha
The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content...
April 11, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28405624/gm-csf-is-not-essential-for-experimental-autoimmune-encephalomyelitis-but-promotes-brain-targeted-disease
#20
Emily R Pierson, Joan M Goverman
Experimental autoimmune encephalomyelitis (EAE) has been used as an animal model of multiple sclerosis to identify pathogenic cytokines that could be therapeutic targets. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is the only cytokine reported to be essential for EAE. We investigated the role of GM-CSF in EAE in C3HeB/FeJ mice that uniquely exhibit extensive brain and spinal cord inflammation. Unexpectedly, GM-CSF-deficient C3HeB/FeJ mice were fully susceptible to EAE because IL-17 activity compensated for the loss of GM-CSF during induction of spinal cord-targeted disease...
April 6, 2017: JCI Insight
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