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https://www.readbyqxmd.com/read/29665440/mri-compatible-ms2-nanoparticles-designed-to-cross-the-blood-brain-barrier-providing-a-path-towards-tinnitus-treatment
#1
Aaron K Apawu, Stephanie M Curley, Angela R Dixon, Mirabela Hali, Moaz Sinan, Rod D Braun, James Castracane, Anthony T Cacace, Magnus Bergkvist, Avril Genene Holt
Fundamental challenges of targeting specific brain regions for treatment using pharmacotherapeutic nanoparticle (NP) carriers include circumventing the blood-brain-barrier (BBB) and tracking delivery. Angiopep-2 (AP2) has been shown to facilitate the transport of large macromolecules and synthetic nanoparticles across the BBB. Thus, conjugation of AP2 to an MS2 bacteriophage based NP should also permit transport across the BBB. We have fabricated and tested a novel MS2 capsid-based NP conjugated to the ligand AP2...
April 14, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29665383/impact-of-aging-alzheimer-s-disease-and-parkinson-s-disease-on-the-blood-brain-barrier-transport-of-therapeutics
#2
Yijun Pan, Joseph A Nicolazzo
Older people are at greater risk of medicine-induced toxicities resulting from either increased drug sensitivity or age-related pharmacokinetic changes. The scenario is further complicated with the two most prevalent age-related neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD). With aging, AD and PD, there is growing evidence of altered structure and function of the blood-brain barrier (BBB), including modifications to tight junctions and efflux transporters, such as P-glycoprotein...
April 14, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29665111/inhibition-of-transient-receptor-potential-vanilloid-4-decreases-the-expressions-of-caveolin-1-and-caveolin-2-after-focal-cerebral-ischemia-and-reperfusion-in-rats
#3
Hui Xie, Wei-Cheng Lu
This study aimed to investigate the effects of transient receptor potential vanilloid 4 (TRPV4) inhibition on blood-brain barrier (BBB) integrity and the expressions of caveolae structural proteins caveolin-1 and caveolin-2 in rats with focal cerebral ischemia and reperfusion. BBB permeability was assessed by Evans blue extravasation. The mRNA and protein expressions of caveolin-1 and caveolin-2 were determined by RT-PCR, Western blot and immunohistochemistry assays. We found that BBB permeability significantly increased and reaches its peak at 72 h of reperfusion in cerebral ischemia-reperfusion rats and is able to be ameliorated by administration of HC-067047, an antagonist of TRPV4...
April 17, 2018: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/29665077/gliovascular-changes-precede-white-matter-damage-and-long-term-disorders-in-juvenile-mild-closed-head-injury
#4
Beatriz Rodriguez-Grande, Andre Obenaus, Aleksandra Ichkova, Justine Aussudre, Thomas Bessy, Elodie Barse, Bassem Hiba, Gwénaëlle Catheline, Grégory Barrière, Jerome Badaut
Traumatic brain injury (TBI) is a leading cause of hospital visits in pediatric patients and often leads to long-term disorders even in cases of mild severity. White matter (WM) alterations are commonly observed in patients months or years after the injury assessed by magnetic resonance imaging (MRI), but little is known about WM pathophysiology early after mild pediatric TBI. To evaluate the status of the gliovascular unit in this context, mild TBI was induced in postnatal-day 17 mice using a closed head injury model with two grades of severity (G1, G2)...
April 17, 2018: Glia
https://www.readbyqxmd.com/read/29663890/methodologies-related-to-computational-models-in-view-of-developing-anti-alzheimer-drugs-an-overview
#5
Kirtee Baheti, Mayura Ajay Kale
BACKGROUND: Since last two decades, there has been more focus on the development strategies related to Anti-Alzheimer's drug research. This may be attributed to the fact that most of the Alzheimer's cases are still mostly unknown except for a few cases, where genetic differences have been identified. With the progress of the disease, the symptoms involve intellectual deterioration, memory impairment, abnormal personality and behavioural patterns, confusion, aggression, mood swings, irritability Current therapies available for this disease give only symptomatic relief and do not focus on manipulations of biololecular processes...
April 17, 2018: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/29660609/aflatoxin-b-1-contaminated-diet-disrupts-the-blood-brain-barrier-and-affects-fish-behavior-involvement-of-neurotransmitters-in-brain-synaptosomes
#6
Matheus D Baldissera, Carine F Souza, Carla Cristina Zeppenfeld, Sharine N Descovi, Karen Luise S Moreira, Maria Izabel U M da Rocha, Marcelo L da Veiga, Aleksandro S da Silva, Bernardo Baldisserotto
It is known that the cytotoxic effects of aflatoxin B1 (AFB1 ) in endothelial cells of the blood-brain barrier (BBB) are associated with behavioral dysfunction. However, the effects of a diet contaminated with AFB1 on the behavior of silver catfish remain unknown. Thus, the aim of this study was to evaluate whether an AFB1 -contaminated diet (1177 ppb kg feed-1 ) impaired silver catfish behavior, as well as whether disruption of the BBB and alteration of neurotransmitters in brain synaptosomes are involved...
April 4, 2018: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29660499/modulating-membrane-fluidity-corrects-batten-disease-phenotypes-in-vitro-and-in-vivo
#7
Mark L Schultz, Luis Tecedor, Elena Lysenko, Shyam Ramachandran, Colleen S Stein, Beverly L Davidson
The neuronal ceroid lipofuscinoses are a class of inherited neurodegenerative diseases characterized by the accumulation of autofluorescent storage material. The most common neuronal ceroid lipofuscinosis has juvenile onset with rapid onset blindness and progressive degeneration of cognitive processes. The juvenile form is caused by mutations in the CLN3 gene, which encodes the protein CLN3. While mouse models of Cln3 deficiency show mild disease phenotypes, it is apparent from patient tissue- and cell-based studies that its loss impacts many cellular processes...
April 13, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29655691/functionalized-liposomes-and-phytosomes-loading-annona-muricata-l-aqueous-extract-potential-nanoshuttles-for-brain-delivery-of-phenolic-compounds
#8
Simona Mancini, Luca Nardo, Maria Gregori, Inês Ribeiro, Francesco Mantegazza, Cristina Delerue-Matos, Massimo Masserini, Clara Grosso
BACKGROUND: Multi-target drugs have gained significant recognition for the treatment of multifactorial diseases such as depression. Under a screening study of multi-potent medicinal plants with claimed antidepressant-like activity, the phenolic-rich Annona muricata aqueous extract (AE) emerged as a moderate monoamine oxidase A (hMAO-A) inhibitor and a strong hydrogen peroxide (H2 O2 ) scavenger. PURPOSE: In order to protect this extract from gastrointestinal biotransformation and to improve its permeability across the blood-brain barrier (BBB), four phospholipid nanoformulations of liposomes and phytosomes functionalized with a peptide ligand promoting BBB crossing were produced...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29653366/bufalin-inhibits-glioblastoma-growth-by-promoting-proteasomal-degradation-of-the-na-k-atpase-%C3%AE-1-subunit
#9
Yu-Long Lan, Xun Wang, Jia-Cheng Lou, Jin-Shan Xing, Zhen-Long Yu, Hongjin Wang, Shuang Zou, Xiaochi Ma, Bo Zhang
Chansu is a traditional Chinese medicine that is generally recognized as a specific inhibitor of Na+ /K+ -ATPase. Bufalin, an active component of Chansu, is an endogenous steroid hormone with great potential as a cancer treatment. However, the mechanism by which it exerts its antitumor activity requires further research. Currently, the α1 subunit of Na+ /K+ -ATPase (ATP1A1) is known to exert important roles in tumorigenesis, and the precise mechanisms underlying the effect of Bufalin on the Na+ /K+ -ATPase α1 subunit was therefore investigated in this study to determine its role in glioblastoma treatments...
April 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29652199/the-role-and-mechanism-of-borneol-to-open-the-blood-brain-barrier
#10
Tao Wu, Aiqin Zhang, Hongyang Lu, Qiaoyuan Cheng
BACKGROUND: The blood-brain barrier (BBB) is the greatest challenge in the treatment of intracranial malignant tumors. OBJECTIVE: The aim of this study is to determine the role of borneol in opening the BBB and elucidate the underlying mechanisms. MATERIALS AND METHODS: Twenty Sprague-Dawley (SD) rats were randomized into borneol group intragastrically administered with 10% borneol corn oil (2 mL/kg) and control group. After 30 minutes, 2% Evans blue (4 mL/kg) was injected...
April 1, 2018: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/29651960/targeting-brain-tumors-with-nanomedicines-overcoming-challenges-of-blood-brain-barrier
#11
Nagendra S Ningaraj, Polluru L Reddy, Divya Khaitan
This review elucidates ongoing research, which show improved delivery of anticancer drugs alone and/ or enclosed in carriers collectively called nanomedicines to cross the Blood brain barrier (BBB) / blood-brain tumor barrier (BTB) to kill tumor cells and impact patient survival. We highlighted various advances in understanding the mechanism of BTB function that impact on anticancer therapeutics delivery. We discussed latest breakthroughs in developing pharmaceutical strategies, including nanomedicines and delivering them across BTB for brain tumor management and treatment...
April 12, 2018: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/29651876/novel-hits-for-acetylcholinesterase-inhibition-derived-by-docking-based-screening-on-zinc-database
#12
Irini Doytchinova, Mariyana Atanasova, Iva Valkova, Georgi Stavrakov, Irena Philipova, Zvetanka Zhivkova, Dimitrina Zheleva-Dimitrova, Spiro Konstantinov, Ivan Dimitrov
The inhibition of the enzyme acetylcholinesterase (AChE) increases the levels of the neurotransmitter acetylcholine and symptomatically improves the affected cognitive function. In the present study, we searched for novel AChE inhibitors by docking-based virtual screening of the standard lead-like set of ZINC database containing more than 6 million small molecules using GOLD software. The top 10 best-scored hits were tested in vitro for AChE affinity, neurotoxicity, GIT and BBB permeability. The main pharmacokinetic parameters like volume of distribution, free fraction in plasma, total clearance, and half-life were predicted by previously derived models...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29651705/rat-cerebrospinal-fluid-treatment-method-through-cisterna-cerebellomedullaris-injection
#13
Thainá Garbino Dos Santos, Mery Stéfani Leivas Pereira, Diogo Losch Oliveira
Drugs that lack the ability to cross the blood-brain barrier (BBB) need to be placed directly into the central nervous system. Our laboratory studies the involvement of the glutamatergic system in the aggressiveness of glioma, and some ligands of glutamate receptors cannot permeate the BBB. Here, glioma-implanted rats were treated by a technique that delivers ligands directly into the cerebrospinal fluid by puncture into the cisterna cerebellomedullaris. Rats were anesthetized and fixed in a rodent stereotactic device...
April 12, 2018: Neuroscience Bulletin
https://www.readbyqxmd.com/read/29650684/epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-for-central-nervous-system-metastases-from-non-small-cell-lung-cancer
#14
REVIEW
Manmeet S Ahluwalia, Kevin Becker, Benjamin P Levy
Central nervous system (CNS) metastases are a common complication in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), resulting in a poor prognosis and limited treatment options. Treatment of CNS metastases requires a multidisciplinary approach, and the optimal treatment options and sequence of therapies are yet to be established. Many systemic therapies have poor efficacy in the CNS due to the challenges of crossing the blood-brain barrier (BBB), creating a major unmet need for the development of agents with good BBB-penetrating biopharmaceutical properties...
April 12, 2018: Oncologist
https://www.readbyqxmd.com/read/29650289/optimization-of-dipeptidic-inhibitors-of-cathepsin-l-for-improved-toxoplasma-gondii-selectivity-and-cns-permeability
#15
Jeffery D Zwicker, Nicolas A Diaz, Alfredo J Guerra, Paul D Kirchhoff, Bo Wen, Duxin Sun, Vern B Carruthers, Scott D Larsen
The neurotropic protozoan Toxoplasma gondii is the second leading cause of death due to foodborne illness in the US, and has been designated as one of five neglected parasitic infections by the Center for Disease Control and Prevention. Currently, no treatment options exist for the chronic dormant-phase Toxoplasma infection in the central nervous system (CNS). T. gondii cathepsin L (TgCPL) has recently been implicated as a novel viable target for the treatment of chronic toxoplasmosis. In this study, we report the first body of SAR work aimed at developing potent inhibitors of TgCPL with selectivity vs the human cathepsin L...
March 9, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29649465/therapeutic-time-window-and-regulation-of-autophagy-by-mild-hypothermia-after-intracerebral-hemorrhage-in-rats
#16
Feifei Song, Cen Guo, Yang Geng, Xuqing Wu, Wei Fan
Although recent studies have shown that mild hypothermia has neuroprotective effects on intracerebral hemorrhage (ICH), the therapeutic time window of the therapy and the role of autophagy as a potential neuroprotective mechanism remain unclear. This study was aimed to investigate the appropriate time window of mild hypothermia and the regulation of autophagy during the treatment in a rat model of autologous blood-injected ICH injury. The rats were divided into Sham, normothermic (NT) and hypothermic (HT) groups...
April 9, 2018: Brain Research
https://www.readbyqxmd.com/read/29649307/bilateral-carotid-artery-stenosis-causes-unexpected-early-changes-in-brain-extracellular-matrix-and-blood-brain-barrier-integrity-in-mice
#17
Jill M Roberts, Michael E Maniskas, Gregory J Bix
Bilateral carotid artery stenosis (BCAS) is one experimental model of vascular dementia thought to preferentially impact brain white matter. Indeed, few studies report hippocampal and cortical pathology prior to 30 days post-stenosis; though it is unclear whether those studies examined regions outside the white matter. Since changes in the blood-brain barrier (BBB) permeability precede more overt brain pathology in various diseases, we hypothesized that changes within the BBB and/or BBB-associated extracellular matrix (ECM) could occur earlier after BCAS in the hippocampus, cortex and striatum and be a precursor of longer term pathology...
2018: PloS One
https://www.readbyqxmd.com/read/29648978/fgf21-protects-the-blood-brain-barrier-by-upregulating-ppar%C3%AE-via-fgfr1-%C3%AE-klotho-following-traumatic-brain-injury
#18
Jun Chen, Jian Hu, Huan Liu, Ye Xiong, Yuchi Zou, Wenting Huang, Mingjie Shao, Jiamin Wu, Li Yu, Xiaojie Wang, Xue Wang, Li Lin
Blood-brain barrier (BBB) disruption and dysfunction result in brain edema, which is responsible for more than half of all deaths after severe traumatic brain injury (TBI). Fibroblast growth factor 21 (FGF21) has a potential neuroprotective function in the brain. However, the effects and underlying possible mechanism of action on BBB integrity following TBI remain unknown. The purpose of the current study was to determine the effects of FGF21 on BBB protection and TBI treatment. The effects of recombinant human FGF21 (rhFGF21) on BBB integrity and on tight junction and adherens junction proteins were investigated both in a TBI mouse model and an in vitro BBB disruption model established with TNF-α-induced human brain microvascular endothelial cells (HBMECs)...
March 6, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29648973/male-and-female-mice-exhibit-divergent-responses-of-the-cortical-vasculature-to-traumatic-brain-injury
#19
Amandine Jullienne, Arjang Salehi, Bethann Affeldt, Mohsen Baghchechi, Elizabeth Haddad, Angela Avitua, Mark Walsworth, Isabelle Enjalric, Mary Hamer, Sonali Bhakta, Jiping Tang, John Zhang, William J Pearce, Andre Obenaus
We previously reported that traumatic brain injuries (TBI) alter cerebrovasculature near the injury site in rats, followed by revascularization over a 2-week period. Here, we tested our hypothesis that male and female adult mice have differential cerebrovascular responses following a moderate controlled cortical impact (CCI). Using in vivo magnetic resonance imaging (MRI), a new technique called vessel painting, and immunohistochemistry, we found no differences between males and females in lesion volume, neurodegeneration, blood-brain barrier (BBB) alteration and microglia activation...
March 5, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29629621/pdgfr-%C3%AE-restores-blood-brain-barrier-functions-in-a-mouse-model-of-focal-cerebral-ischemia
#20
Jie Shen, Guihua Xu, Runxiu Zhu, Jun Yuan, Yoko Ishii, Takeru Hamashima, Takako Matsushima, Seiji Yamamoto, Yusuke Takatsuru, Junichi Nabekura, Masakiyo Sasahara
Although platelet-derived growth factor receptor beta (PDGFR-β) mediates the recruitment of vascular pericytes into ischemic lesion to restore the blood-brain barrier (BBB) dysfunction, its mechanisms still remain elusive . Compared with control PDGFR-βfloxed / floxed mice (Floxed), postnatally induced systemic PDGFR-β knockout mice (Esr-KO) not only showed severe brain edema, neurologic functional deficits, decreased expression of tight junction (TJ) proteins, abundant endothelial transcytosis, and deformed TJs in the BBB, but also showed reduced expression of transforming growth factor-β (TGF-β) protein after photothrombotic middle cerebral artery occlusion (MCAO)...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
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