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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
#1
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
#2
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 10, 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
#3
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
https://www.readbyqxmd.com/read/28397188/brain-targeted-polymers-for-gene-delivery-in-the-treatment-of-brain-diseases
#4
REVIEW
Yifei Lu, Chen Jiang
Gene therapies have become a promising strategy for treating neurological disorders, such as brain cancer and neurodegenerative diseases, with the help of molecular biology interpreting the underlying pathological mechanisms. Successful cellular manipulation against these diseases requires efficient delivery of nucleic acids into brain and further into specific neurons or cancer cells. Compared with viral vectors, non-viral polymeric carriers provide a safer and more flexible way of gene delivery, although suffering from significantly lower transfection efficiency...
April 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28379213/energy-dense-diet-triggers-changes-in-gut-microbiota-reorganization-of-gut%C3%A2-brain-vagal-communication-and-increases-body-fat-accumulation
#5
Alexandra C Vaughn, Erin M Cooper, Patricia M DiLorenzo, Levi J O'Loughlin, Michael E Konkel, James H Peters, Andras Hajnal, Tanusree Sen, Sun Hye Lee, Claire B de La Serre, Krzysztof Czaja
Obesity is associated with consumption of energy-dense diets and development of systemic inflammation. Gut microbiota play a role in energy harvest and inflammation and can influence the change from lean to obese phenotypes. The nucleus of the solitary tract (NTS) is a brain target for gastrointestinal signals modulating satiety and alterations in gut-brain vagal pathway may promote overeating and obesity. Therefore, we tested the hypothesis that high-fat diet‑induced changes in gut microbiota alter vagal gut-brain communication associated with increased body fat accumulation...
2017: Acta Neurobiologiae Experimentalis
https://www.readbyqxmd.com/read/28372121/accurate-simulation-of-transcranial-ultrasound-propagation-for-ultrasonic-neuromodulation-and-stimulation
#6
James L B Robertson, Ben T Cox, J Jaros, Bradley E Treeby
Non-invasive, focal neurostimulation with ultrasound is a potentially powerful neuroscientific tool that requires effective transcranial focusing of ultrasound to develop. Time-reversal (TR) focusing using numerical simulations of transcranial ultrasound propagation can correct for the effect of the skull, but relies on accurate simulations. Here, focusing requirements for ultrasonic neurostimulation are established through a review of previously employed ultrasonic parameters, and consideration of deep brain targets...
March 2017: Journal of the Acoustical Society of America
https://www.readbyqxmd.com/read/28358814/dysfunctions-of-the-basal-ganglia-cerebellar-thalamo-cortical-system-produce-motor-tics-in-tourette-syndrome
#7
Daniele Caligiore, Francesco Mannella, Michael A Arbib, Gianluca Baldassarre
Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. Building on such evidence, this article proposes a computational model of the basal ganglia-cerebellar-thalamo-cortical system to study how motor tics are generated in Tourette syndrome. In particular, the model: (i) reproduces the main results of recent experiments about the involvement of the basal ganglia-cerebellar-thalamo-cortical system in tic generation; (ii) suggests an explanation of the system-level mechanisms underlying motor tic production: in this respect, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production; (iii) furnishes predictions on the amount of tics generated when striatal dopamine increases and when the cortex is externally stimulated...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28351667/pyrilamine-sensitive-proton-coupled-organic-cation-h-oc-antiporter-for-brain-specific-drug-delivery
#8
Xinyi Wang, Bowen Qi, Huifang Su, Jianbo Li, Xun Sun, Qin He, Yao Fu, Zhirong Zhang
Blood-brain barrier (BBB) represents the greatest challenge that hampers therapeutic molecules entering the brain. Here, we described a novel brain-specific delivery strategy targeting to pyrilamine-sensitive H(+)/OC antiporter to facilitate therapeutic molecules cross the BBB and penetrate into the brain. In this study, four cyclic tertiary amines were selected as the brain-targeting moieties to modify naproxen (NP), a non-steroidal anti-inflammatory drug. The obtained NP conjugates displayed cell uptake efficiencies over 144-fold higher than that of unmodified NP in endothelial cells...
March 27, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28326445/the-role-of-nonhuman-primate-models-in-the-development-of-cell-based-therapies-for-parkinson-s-disease
#9
REVIEW
Scott C Vermilyea, Marina E Emborg
Through the course of over three decades, nonhuman primate (NHP) studies on cell-based therapies (CBTs) for Parkinson's disease (PD) have provided insight into the feasibility, safety and efficacy of the approach, methods of cell collection and preparation, cell viability, as well as potential brain targets. Today, NHP research continues to be a vital source of information for improving cell grafts and analyzing how the host affects graft survival, integration and function. Overall, this article aims to discuss the role that NHP models of PD have played in CBT development and highlights specific issues that need to be considered to maximize the value of NHP studies for the successful clinical translation of CBTs...
March 22, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28315351/-3-h-bmt-046091-a-potent-and-selective-radioligand-to-determine-aak1-distribution-and-target-engagement
#10
Justin V Louis, Yifeng Lu, Rick Pieschl, Yung Tian, Yang Hong, Kumaran Dandapani, Sreenivasulu Naidu, Reeba K Vikramadithyan, Carolyn Dzierba, Sarat Kumar Sarvasiddhi, Susheel J Nara, Joanne Bronson, John E Macor, Charlie Albright, Walter Kostich, Yu-Wen Li
Adaptor-associated kinase 1 (AAK1), a member of the Ark1/Prk1 family of serine/threonine kinases, plays a role in modulating clatherin coated endocytosis of specific surface receptors. We have demonstrated that AAK1 inhibitors are efficacious in rodent models of neuropathic pain (Kostich et al., 2016). Here we have characterized the binding properties and distribution pattern of the tritiated AAK1 radioligand, [(3)H]BMT-046091, in rodents and cynomolgus monkeys, and used the radioligand to measure the brain target occupancy following systemic administration of AAK1 inhibitors...
March 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28285172/multifunctional-luv-liposomes-decorated-for-bbb-and-amyloid-targeting-b-in-vivo-brain-targeting-potential-in-wild-type-and-app-ps1-mice
#11
Konstantina Papadia, Anastasios D Giannou, Eleni Markoutsa, Christian Bigot, Greejte Vanhoute, Spyridon Mourtas, Annemie Van der Linded, Georgios T Stathopoulos, Sophia G Antimisiaris
Multifunctional liposomes (mf-LIPs) having a curcumin-lipid ligand (to target amyloids) together with two ligands to target the transferrin, and the low-density apolipoprotein receptor of the blood-brain-barrier (BBB) on their surface, were previously studied (in vitro) as potential theranostic systems for Alzheimer's disease (AD) (Papadia et al., 2017, Eur. J. Pharm. Sciences; 101:140-148). Herein, the targeting potential of mf-LIPs was compared to that of BBB-LIPs (liposomes having only the two BBB-specific ligands) in FVB mice (normal), as well as in double transgenic mice (APP/PS1) and their corresponding littermates (WT), by live-animal (in vivo) and explanted organ (ex vivo) imaging...
March 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28273176/pulsatile-desynchronizing-delayed-feedback-for-closed-loop-deep-brain-stimulation
#12
Oleksandr V Popovych, Borys Lysyansky, Michael Rosenblum, Arkady Pikovsky, Peter A Tass
High-frequency (HF) deep brain stimulation (DBS) is the gold standard for the treatment of medically refractory movement disorders like Parkinson's disease, essential tremor, and dystonia, with a significant potential for application to other neurological diseases. The standard setup of HF DBS utilizes an open-loop stimulation protocol, where a permanent HF electrical pulse train is administered to the brain target areas irrespectively of the ongoing neuronal dynamics. Recent experimental and clinical studies demonstrate that a closed-loop, adaptive DBS might be superior to the open-loop setup...
2017: PloS One
https://www.readbyqxmd.com/read/28269604/effects-of-high-frequency-rtms-on-sleep-deprivation-a-pilot-study
#13
D P Martinez-Cancino, J Azpiroz-Leehan, L Jimenez-Angeles, A Garcia-Quintanar, R Santana-Miranda
Transcranial magnetic stimulation is a neurostimulation technique which has the potential to serve as a unique research tool for investigating a wide variety of fields in cognitive neuroscience. TMS has been approved by the FDA to serve as a treatment to depression and has also been used to evaluate its effects among several conditions such as Alzheimer, Parkinson disease, chronic pain and stroke. High frequency TMS has been previously used with the intention to measure and modulate the negative effects of sleep deprivation in cognitive performance, but there is no consensus about the ideal protocol yet...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28254591/a-small-leak-will-sink-the-brain-targeted-c1-c2-patching
#14
Thomas Decramer, Pieter Jan Van Dyck-Lippens, Tom P Franken, Philippe Demaerel, Johannes van Loon, Tom Theys
BACKGROUND: Spontaneous intracranial hypotension (SIH) syndrome results from spontaneous spinal CSF leaks. The first treatment of choice consists of lumbar epidural blood patching. If this fails further imaging is mandatory to explore the possibility of targeted therapy. CASE DESCRIPTION: We describe a case of a 50-year old woman who developed spontaneous intracranial hypotension after minor blunt cervical trauma, complicated with bilateral subdural hematomas. Two lumbar epidural blood patches were unsuccessful...
February 27, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28244991/oligonucleotide-therapies-for-disorders-of-the-nervous-system
#15
Olga Khorkova, Claes Wahlestedt
Oligonucleotide therapies are currently experiencing a resurgence driven by advances in backbone chemistry and discoveries of novel therapeutic pathways that can be uniquely and efficiently modulated by the oligonucleotide drugs. A quarter of a century has passed since oligonucleotides were first applied in living mammalian brain to modulate gene expression. Despite challenges in delivery to the brain, multiple oligonucleotide-based compounds are now being developed for treatment of human brain disorders by direct delivery inside the blood brain barrier (BBB)...
March 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28243600/systematic-approach-for-the-formulation-and-optimization-of-solid-lipid-nanoparticles-of-efavirenz-by-high-pressure-homogenization-using-design-of-experiments-for-brain-targeting-and-enhanced-bioavailability
#16
Shweta Gupta, Rajesh Kesarla, Narendra Chotai, Ambikanandan Misra, Abdelwahab Omri
The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28227862/effects-of-high-frequency-rtms-on-sleep-deprivation-a-pilot-study
#17
D P Martinez-Cancino, J Azpiroz-Leehan, L Jimenez-Angeles, A Garcia-Quintanar, R Santana-Miranda, D P Martinez-Cancino, J Azpiroz-Leehan, L Jimenez-Angeles, A Garcia-Quintanar, R Santana-Miranda, A Garcia-Quintanar, L Jimenez-Angeles, R Santana-Miranda, J Azpiroz-Leehan, D P Martinez-Cancino
Transcranial magnetic stimulation is a neurostimulation technique which has the potential to serve as a unique research tool for investigating a wide variety of fields in cognitive neuroscience. TMS has been approved by the FDA to serve as a treatment to depression and has also been used to evaluate its effects among several conditions such as Alzheimer, Parkinson disease, chronic pain and stroke. High frequency TMS has been previously used with the intention to measure and modulate the negative effects of sleep deprivation in cognitive performance, but there is no consensus about the ideal protocol yet...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28215668/potential-of-surfactant-coated-nanoparticles-to-improve-brain-delivery-of-arylsulfatase-a
#18
Tilman Schuster, Astrid Mühlstein, Claudia Yaghootfam, Olga Maksimenko, Elena Shipulo, Svetlana Gelperina, Jörg Kreuter, Volkmar Gieselmann, Ulrich Matzner
The lysosomal storage disorder (LSD) metachromatic leukodystrophy (MLD) is caused by a deficiency of the soluble, lysosomal hydrolase arylsulfatase A (ASA). The disease is characterized by accumulation of 3-O-sulfogalactosylceramide (sulfatide), progressive demyelination of the nervous system and premature death. Enzyme replacement therapy (ERT), based on regular intravenous injections of recombinant functional enzyme, is in clinical use for several LSDs. For MLD and other LSDs with central nervous system (CNS) involvement, however, ERT is limited by the blood-brain barrier (BBB) restricting transport of therapeutic enzymes from the blood to the brain...
February 16, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28205340/predictive-modeling-of-eeg-time-series-for-evaluating-surgery-targets-in-epilepsy-patients
#19
Andreas Steimer, Michael Müller, Kaspar Schindler
During the last 20 years, predictive modeling in epilepsy research has largely been concerned with the prediction of seizure events, whereas the inference of effective brain targets for resective surgery has received surprisingly little attention. In this exploratory pilot study, we describe a distributional clustering framework for the modeling of multivariate time series and use it to predict the effects of brain surgery in epilepsy patients. By analyzing the intracranial EEG, we demonstrate how patients who became seizure free after surgery are clearly distinguished from those who did not...
February 16, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28197551/ephrina5-signaling-is-required-for-the-distinctive-targeting-of-raphe-serotonin-neurons-in-the-forebrain
#20
Teng Teng, Afsaneh Gaillard, Aude Muzerelle, Patricia Gaspar
Serotonin (5-HT) neurotransmission in the brain relies on a widespread axon terminal network originating from the hindbrain raphe nuclei. These projections are topographically organized such that the dorsal (DR), and median raphe (MnR) nuclei have different brain targets. However, the guidance molecules involved in this selective targeting in development are unknown. Here, we show the implication of ephrinA5 signaling in this process. We find that the EphA5 gene is selectively expressed in a subset of 5-HT neurons during embryonic and postnatal development...
January 2017: ENeuro
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