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https://www.readbyqxmd.com/read/28326445/the-role-of-nonhuman-primate-models-in-the-development-of-cell-based-therapies-for-parkinson-s-disease
#1
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
#2
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 14, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28195170/quantifying-cerebral-contributions-to-pain-beyond-nociception
#13
Choong-Wan Woo, Liane Schmidt, Anjali Krishnan, Marieke Jepma, Mathieu Roy, Martin A Lindquist, Lauren Y Atlas, Tor D Wager
Cerebral processes contribute to pain beyond the level of nociceptive input and mediate psychological and behavioural influences. However, cerebral contributions beyond nociception are not yet well characterized, leading to a predominant focus on nociception when studying pain and developing interventions. Here we use functional magnetic resonance imaging combined with machine learning to develop a multivariate pattern signature-termed the stimulus intensity independent pain signature-1 (SIIPS1)-that predicts pain above and beyond nociceptive input in four training data sets (Studies 1-4, N=137)...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28193538/multifunctional-luv-liposomes-decorated-for-bbb-and-amyloid-targeting-a-in-vitro-proof-of-concept
#14
Konstantina Papadia, Eleni Markoutsa, Spyridon Mourtas, Anastassios D Giannou, Barabara La Ferla, Fransesco Nicotra, Mario Salmona, Pavlos Klepetsanis, Georgios T Stathopoulos, Sophia G Antimisiaris
Multifunctional LUV liposomes (mf-LIPs) were developed, having a curcumin-lipid ligand (TREG) with affinity towards amyloid species, together with ligands to target the transferrin and the LDL receptors of the blood-brain-barrier (BBB), on their surface. mf-LIPs were evaluated for their brain targeting, on hCMEC/D3 monolayers, and for their ability to inhibit Aβ-peptide aggregation. The transport of mf-LIP across hCMEC/D3 monolayers was similar to that of BBB-LIPs, indicating that the presence of TREG on their surface does not reduce their brain targeting potential...
April 1, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28165806/enhancing-both-oral-bioavailability-and-brain-penetration-of-puerarin-using-borneol-in-combination-with-preparation-technologies
#15
Tao Yi, Dandan Tang, Fan Wang, Jiqiong Zhang, Jiao Zhang, Jirui Wang, Xiaoyu Xu, Jifen Zhang
Now there are few good oral preparations of puerarin used in cerebrovascular diseases because of its poor oral absorption caused by the low water solubility and the poor penetration into brain. In this study, three oral formulations of puerarin, nanocrystals suspension (NCS), inclusion compounds solution (ICS) and self-microemulsifying drug delivery system (SMEDDS) were prepared with borneol as an oral brain-targeting enhancer. A rat syngeneic in vitro model of the brain-blood barrier (BBB) was established to investigate effects of borneol on the permeability of puerarin across the BBB...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28156175/docosahexaenoic-acid-mediated-targeted-and-sustained-brain-delivery-of-curcumin-microemulsion
#16
Rajshree L Shinde, Padma V Devarajan
We disclose microemulsions (ME) of curcumin (CUR) with docosahexaenoic acid (DHA)-rich oil (CUR DHA ME) for targeted delivery to the brain. MEs of CUR (5 mg/mL) with and without DHA-rich oil (CUR Capmul ME) suitable for intravenous and intranasal administration exhibited negative zeta potential, globule size  <20 nm and good stability. Following intravenous delivery MEs exhibited high brain concentration with CUR DHA ME exhibiting a 2.8-fold higher Cmax than CUR solution. Furthermore, high and sustained concentration was demonstrated even at 24 h, which was 8- and 2-fold higher than CUR solution and CUR Capmul ME, respectively...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28156162/contribution-of-both-olfactory-and-systemic-pathways-for-brain-targeting-of-nimodipine-loaded-lipo-pluronics-micelles-in-vitro-characterization-and-in-vivo-biodistribution-study-after-intranasal-and-intravenous-delivery
#17
COMPARATIVE STUDY
Hassan M Rashed, Rehab N Shamma, Emad B Basalious
Nimodipine (NM) is the only FDA-approved drug for treating subarachnoid hemorrhage induced vasospasm. NM has poor oral bioavailability (5-13%) due to its low aqueous solubility, and extensive first pass metabolism. The objective of this study is to develop radiolabeled NM-loaded LPM and to test its ability prolong its circulation time, reduce its frequency of administration and eventually target it to the brain tissue. NM was radiolabeled with (99m)Tc by direct labeling method using sodium dithionite. Different reaction conditions that affect the radiolabeling yield were studied...
November 2016: Drug Delivery
https://www.readbyqxmd.com/read/28153761/apoe-modified-solid-lipid-nanoparticles-a-feasible-strategy-to-cross-the-blood-brain-barrier
#18
R Dal Magro, F Ornaghi, I Cambianica, S Beretta, F Re, C Musicanti, R Rigolio, E Donzelli, A Canta, E Ballarini, G Cavaletti, P Gasco, G Sancini
Solid lipid nanoparticles (SLN) are colloidal drug delivery systems characterized by higher entrapment efficiency, good scalability of the preparation process and increased sustained prolonged release of the payload compared to other nanocarriers. The possibility to functionalize the surface of SLN with ligands to achieve a site specific targeting makes them attractive to overcome the limited blood-brain barrier (BBB) penetration of therapeutic compounds. SLN are prepared for brain targeting by exploiting the adaptability of warm microemulsion process for the covalent surface modification with an Apolipoprotein E-derived peptide (SLN-mApoE)...
March 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28151022/enhanced-blood-brain-barrier-transport-of-vinpocetine-by-oral-delivery-of-mixed-micelles-in-combination-with-a-message-guider
#19
Jiaojiao Ding, Yujiao Sun, Jinfeng Li, Huimin Wang, Shirui Mao
The blood brain barrier represents an insurmountable obstacle for the therapy of central nervous system related diseases. Polymeric micelles have many desirable properties for brain targeting by oral delivery but the stability and targeting efficiency needs to be improved. In this study, it was demonstrated that binary micelle system can compensate the drawbacks of mono system by preparing mixed micelles in combination with PEG based copolymers. Here we explored a brain targeting drug delivery system via facile approaches using P123 based mixed micelles in combination with a message guider from traditional Chinese medicine, borneol, for oral delivery...
February 2, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28134808/from-belly-to-brain-targeting-the-ghrelin-receptor-in-appetite-and-food-intake-regulation
#20
REVIEW
Ken Howick, Brendan T Griffin, John F Cryan, Harriët Schellekens
Ghrelin is the only known peripherally-derived orexigenic hormone, increasing appetite and subsequent food intake. The ghrelinergic system has therefore received considerable attention as a therapeutic target to reduce appetite in obesity as well as to stimulate food intake in conditions of anorexia, malnutrition and cachexia. As the therapeutic potential of targeting this hormone becomes clearer, it is apparent that its pleiotropic actions span both the central nervous system and peripheral organs. Despite a wealth of research, a therapeutic compound specifically targeting the ghrelin system for appetite modulation remains elusive although some promising effects on metabolic function are emerging...
January 27, 2017: International Journal of Molecular Sciences
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