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Ali Alawieh, Meredith Andersen, DeAnna L Adkins, Stephen Tomlinson
Since complement activation in the subacute or chronic phase after stroke was recently shown to stimulate neural plasticity, we investigated how complement activation and complement inhibition in the acute phase after murine stroke interacts with subsequent rehabilitation therapy to modulate neuroinflammation and neural remodeling. We additionally investigated how complement and complement inhibition interacts with tissue plasminogen activator (tPA), the other standard of care therapy for stroke, and an FDA preclinical requirement for translation of an experimental stroke therapy...
June 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jessica Fernandes, M Vivek Ghate, Sanchari Basu Mallik, Shaila A Lewis
Saxagliptin (SAX) is dipeptidyl peptidase-4 enzyme inhibitor molecule now explored for its activity in the therapy of Alzheimer's disease. Being extremely hydrophilic, it is unable to permeate the blood-brain barrier by the conventional therapy modalities. Further repurposing the drug, SAX is associated with a reduction in the blood sugar level in the periphery. In the present study, the chitosan-L-valine conjugate was synthesized by carbodiimide chemistry. The conjugate was then used to prepare nanoparticles encapsulating SAX...
June 12, 2018: International Journal of Pharmaceutics
Vicente Martinez, Shu-Ching Hu, Thomas J Foutz, Andew Ko
Holmes tremor (HT) is a rare movement disorder that is typically associated with cerebellar, thalamic or brainstem lesions following a delay. Treatment of HT with deep brain stimulation (DBS) has yielded positive results however; it is unclear which deep brain targets provide optimal therapeutic effects. Here we describe a case report in which a 34 year old man with HT treated successfully with DBS. The ventrointermediate nucleus (VIM) of the thalamus was considered as the initial target. Following electrode placement we determined that the ventral-most electrode contacts were located in the prelemniscal radiations (Raprl)...
2018: Frontiers in Surgery
Fernanda Rodriguez-Otormin, Aroa Duro-Castano, Inmaculada Conejos-Sánchez, María J Vicent
The growing incidence of brain-related pathologies and the problems that undermine the development of efficient and effective treatments have prompted both researchers and the pharmaceutical industry to search for novel therapeutic alternatives. Polymer therapeutics (PT) display properties well suited to the treatment of neuro-related disorders, which help to overcome the many hidden obstacles on the journey to the central nervous system (CNS). The inherent features of PT, derived from drug(s) conjugation, in parallel with the progress in synthesis and analytical methods, the increasing knowledge in molecular basis of diseases, and collected clinical data through the last four decades, have driven the translation from "bench to bedside" for various biomedical applications...
June 14, 2018: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
Anton Harms, Alberto M Heredia-Rizo, G Lorimer Moseley, Raphael Hau, Tasha R Stanton
PURPOSE: To assess the feasibility and clinical impact of brain-targeted treatment (BT; aiming to target sensorimotor processing) in knee osteoarthritis patients attending tertiary care. METHODS: Randomized replicated case series. The study involved three phases, each of 2 weeks duration: (1) no-treatment phase; (2) BT phase (left/right judgments and touch discrimination training); and (3) usual care (education, strengthening, and stretching training). Primary outcomes were: timely recruitment; number of participants completing the interventions; treatment compliance and barriers; follow-up rates; and treatment impact on pain and function...
June 11, 2018: Physiotherapy Theory and Practice
Jennifer Y Li, Tiffany M Schmidt
In addition to its well-known role in pattern vision, light influences a wide range of non-image forming, subconscious visual behaviors including circadian photoentrainment, sleep, mood, learning, and the pupillary light reflex. Each of these behaviors is thought to require input from the M1 subtype of melanopsin-expressing, intrinsically photosensitive retinal ganglion cell (ipRGC). Recent work has demonstrated that the M1 subtype of ipRGC can be further subdivided based on expression of the transcription factor Brn3b...
June 11, 2018: Journal of Comparative Neurology
Ravi Shankar, Monika Joshi, Kamla Pathak
BACKGROUND: Brain is a delicate organ, separated from general circulation and is characterized by the presence of relatively impermeable Blood Brain Barrier (BBB). The BBB maintains homeostasis in the brain thus restricting the entrance of foreign bodies and several molecules from reaching the brain. As a result several promising molecules do not reach the target site and fail to produce in vivo response. Nevertheless, lipid nanoparticles are taken up readily by the brain because of their lipophilic nature...
June 10, 2018: Pharmaceutical Nanotechnology
Huan Wang, Xiaoyi Wang, Cao Xie, Mingfei Zhang, Huitong Ruan, Songli Wang, Kuan Jiang, Fei Wang, Changyou Zhan, Weiyue Lu, Hao Wang
Heptapeptide ATWLPPR (A7R) binds specifically to vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) overexpressed in glioma cells, exhibiting high potential to achieve glioma targeted drug delivery. However, in vivo application of A7R peptide remains challenging due to the poor proteolytic stability and inaccessibility of A7R to the brain. To tackle these problems, we identified a glycosylated A7R derivative to enhance in vivo stability and brain transport efficacy. Our results showed that glycosylation of peptide could efficiently improve stability in serum, traverse the blood-brain barrier (BBB) and be uptaken by glioma cells...
June 6, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Hélène Fe Gleitz, Ai Yin Liao, James R Cook, Samuel F Rowlston, Gabriella Ma Forte, Zelpha D'Souza, Claire O'Leary, Rebecca J Holley, Brian W Bigger
The pediatric lysosomal storage disorder mucopolysaccharidosis type II is caused by mutations in IDS, resulting in accumulation of heparan and dermatan sulfate, causing severe neurodegeneration, skeletal disease, and cardiorespiratory disease. Most patients manifest with cognitive symptoms, which cannot be treated with enzyme replacement therapy, as native IDS does not cross the blood-brain barrier. We tested a brain-targeted hematopoietic stem cell gene therapy approach using lentiviral IDS fused to ApoEII (IDS...
June 8, 2018: EMBO Molecular Medicine
Arsalan S Haqqani, George Thom, Matthew Burrell, Christie E Delaney, Eric Brunette, Ewa Baumann, Caroline Sodja, Anna Jezierski, Carl Webster, Danica B Stanimirovic
The blood-brain barrier (BBB) is a formidable obstacle to the delivery of therapeutics to the brain. Antibodies that bind transferrin receptor, which is enriched in brain endothelial cells, have been shown to cross the BBB and are being developed as fusion proteins to deliver therapeutic cargos to brain targets. Various antibodies have been developed for this purpose and their in vivo evaluation demonstrated that either low affinity or mono-valent receptor binding re-directs their transcellular trafficking away from lysosomal degradation and towards improved exocytosis on the abluminal side of the BBB...
June 7, 2018: Journal of Neurochemistry
Baoyu Chen, Man Luo, Jianming Liang, Chun Zhang, Caifang Gao, Jue Wang, Jianxin Wang, Yongji Li, Desheng Xu, Lina Liu, Ning Zhang, Huijun Chen, Jing Qin
Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N -Acetyl Pro-Gly-Pro (PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles (PGP-SLNs) to facilitate binding to neutrophils in vivo ...
January 2018: Acta Pharmaceutica Sinica. B
Weiyu Chen, Huali Zuo, Enqi Zhang, Li Li, Petra Henrich-Noack, Helen M Cooper, Yujin Qian, Zhi Ping Xu
A delivery platform with highly selective permeability through blood brain barrier (BBB) is essential for brain disease treatment. In this research, we designed and prepared a novel target nano-platform, i.e. layered double hydroxide nanoparticle (LDH) conjugated with targeting peptide-ligand angiopep2 (Ang2) or rabies virus glycoprotein (RVG) via inter-matrix bovine serum albumin (BSA) for brain targeting. In vitro studies show that functionalization with the target ligand significantly increases the delivery efficiency of LDH nanoparticles to the brain endothelial cells (bEnd...
May 25, 2018: ACS Applied Materials & Interfaces
Eleftherios P Pappas, Ioannis Seimenis, Dimitrios Dellios, Georgios Kollias, Kostas I Lampropoulos, Pantelis Karaiskos
This work focuses on MR-related sequence dependent geometric distortions, which are associated with B0 inhomogeneity and patient-induced distortion (susceptibility differences and chemical shift effects), in MR images used in stereotactic radiosurgery (SRS) applications. Emphasis is put on characterizing distortion at target brain areas identified by gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) paramagnetic contrast agent uptake.
 A custom-made phantom for distortion detection was modified to accommodate two small cylindrical inserts, simulating small brain targets...
May 24, 2018: Physics in Medicine and Biology
Rémi Patriat, Scott E Cooper, Yuval Duchin, Jacob Niederer, Christophe Lenglet, Joshua Aman, Michael C Park, Jerrold L Vitek, Noam Harel
The success of deep brain stimulation (DBS) surgeries for the treatment of movement disorders relies on the accurate placement of an electrode within the motor portion of subcortical brain targets. However, the high number of electrodes requiring relocation indicates that today's methods do not ensure sufficient accuracy for all patients. Here, with the goal of aiding DBS targeting, we use 7 Tesla (T) MRI data to identify the functional territories and parcellate the globus pallidus pars interna (GPi) into motor, associative and limbic regions in individual subjects...
May 19, 2018: NeuroImage
Hassan M Rashed, Rehab N Shamma, Hanan A El-Sabagh
Selective receptors imaging using gamma emitting radiopharmaceuticals allows accurate diagnosis and follow up of many brain related disorders. Levetiracetam, a selective SV2A receptor antiepileptic, was successfully radiolabeled using 99m Tc. Different conditions affecting the labelling process were studied and optimum radiochemical yield of 89.8% was obtained. 99m Tc-levetiracetam was effectively formulated and characterized as microemulsion with particle size of 16.34 ± 5.58 nm and polydispersity index of 0...
May 19, 2018: European Journal of Pharmaceutical Sciences
Amarjitsing Rajput, Aditi Bariya, Ahmed Allam, Sarah Othman, Shital B Butani
The purpose of conducting the present research work was to develop resveratrol nanostructured in situ gel for the treatment of Alzheimer's disease. Resveratrol loaded lipid carrier was prepared by melt emulsification-probe sonication method, and the final product was evaluated for particle size (132 ± 11.90 nm), polydispersity index (0.209 ± 0.005), zeta potential (- 23 ± 3.79 mV), drug loading (9.26 ± 3.79%), and entrapment efficiency (74 ± 11.40%). Following incorporation of the resveratrol nanostructured lipid carrier in gellan gum and xanthan gum, in situ gel was formulated and characterized...
May 21, 2018: Drug Delivery and Translational Research
Anam Khan, Mohd Aqil, Syed Sarim Imam, Abdul Ahad, Yasmin Sultana, Asgar Ali, Khalid Khan
The present study was designed to develop and optimize Temozolomide nano lipid chitosan gel delivery (TMZNLCHG) to target the brain through nasal route. The formulation was developed using chitosan as a gelling agent and Vit E: gelucire 44/14 blend as lipid. The formulations were evaluated for particle size, drug loading, morphology, drug release, nasal diffusion, cell line study, and histopathology study. The average particle size, PDI, %EE, loading, drug release, and % permeation were found to be 134 nm, 0...
May 15, 2018: International Journal of Biological Macromolecules
Daniel S Joyce, Beatrix Feigl, Graham Kerr, Luisa Roeder, Andrew J Zele
Parkinson's disease (PD) is characterised by non-motor symptoms including sleep and circadian disruption. Melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGC) transmit light signals to brain areas controlling circadian rhythms and the pupil light reflex. To determine if non-motor symptoms observed in PD are linked to ipRGC dysfunction, we evaluated melanopsin and rod/cone contributions to the pupil response in medicated participants with PD (n = 17) and controls (n = 12)...
May 17, 2018: Scientific Reports
Jung-In Kim, Beom Seok Ahn, Chang Heon Choi, Jong Min Park, So-Yeon Park
BACKGROUND: The aim of this study was to investigate the dosimetric quality in volumetric modulated arc therapy (VMAT) plans with optimal collimator angles that can represent the outline of multiple brain targets. METHODS: Twenty patients with multiple target volumes in the brain cases were selected retrospectively. To better represent the outline of the multiple brain targets, four conformal arc plans were generated for each patient using one full arc with four collimator settings...
May 9, 2018: Radiation Oncology
Brenna P Shortal, Sarah L Reitz, Adeeti Aggarwal, Qing C Meng, Andrew R McKinstry-Wu, Max B Kelz, Alex Proekt
Mechanisms through which anesthetics disrupt neuronal activity are incompletely understood. In order to study anesthetic mechanisms in the intact brain, tight control over anesthetic pharmacology in a genetically and neurophysiologically accessible animal model is essential. Here, we developed a pharmacokinetic model that quantitatively describes propofol distribution into and elimination out of the brain. To develop the model, we used jugular venous catheters to infuse propofol in mice and measured propofol concentration in serial timed brain and blood samples using high performance liquid chromatography (HPLC)...
2018: PloS One
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