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https://www.readbyqxmd.com/read/28212563/progression-of-motor-deficits-in-glioma-bearing-mice-impact-of-cnf1-therapy-at-symptomatic-stages
#1
Eleonora Vannini, Federica Maltese, Francesco Olimpico, Alessia Fabbri, Mario Costa, Matteo Caleo, Laura Baroncelli
Glioblastoma (GBM) is the most aggressive type of brain tumor. In this context, animal models represent excellent tools for the early detection and longitudinal mapping of neuronal dysfunction, that are critical in the preclinical validation of new therapeutic strategies. In a mouse glioma model, we developed sensitive behavioral readouts that allow early recognizing and following neurological symptoms. We injected GL261 cells into the primary motor cortex of syngenic mice and we used a battery of behavioral tests to longitudinally monitor the dysfunction induced by tumor growth...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212190/endothelial-cell-disease-emerging-knowledge-from-cerebral-cavernous-malformations
#2
Maria Grazia Lampugnani, Matteo Malinverno, Elisabetta Dejana
PURPOSE OF REVIEW: Endothelial cells dysfunctions are crucial determinants of several human diseases. We review here the most recent reports on endothelial cell defects in cerebral cavernous malformations (CCMs), particularly focusing on adherens junctions. CCM is a vascular disease that affects specifically the venous microvessels of the central nervous system and which is caused by loss-of-function mutation in any one of the three CCM genes (CCM1, 2 or 3) in endothelial cells. The phenotypic result of these mutations are focal vascular malformations that are permeable and fragile causing neurological symptoms and occasionally haemorrhagic stroke...
February 16, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28211988/intrathecal-enzyme-replacement-therapy-reverses-cognitive-decline-in-mucopolysaccharidosis-type-i
#3
Igor Nestrasil, Elsa Shapiro, Alena Svatkova, Patricia Dickson, Agnes Chen, Amy Wakumoto, Alia Ahmed, Edward Stehel, Sarah McNeil, Curtis Gravance, Elizabeth Maher
Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disease that seriously affects the brain. Severity of neurocognitive symptoms in attenuated MPS subtype (MPS IA) broadly varies partially, due to restricted permeability of blood-brain barrier (BBB) which limits treatment effects of intravenously applied α-L-iduronidase (rhIDU) enzyme. Intrathecal (IT) rhIDU application as a possible solution to circumvent BBB improved brain outcomes in canine models; therefore, our study quantifies effects of IT rhIDU on brain structure and function in an MPS IA patient with previous progressive cognitive decline...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28211814/are-major-dementias-triggered-by-poor-blood-flow-to-the-brain-theoretical-considerations
#4
Jack C de la Torre
There is growing evidence that chronic brain hypoperfusion plays a central role in the development of Alzheimer's disease (AD) long before dyscognitive symptoms or amyloid-β accumulation in the brain appear. This commentary proposes that dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD) may also develop from chronic brain hypoperfusion following a similar but not identical neurometabolic breakdown as AD. The argument to support this conclusion is that chronic brain hypoperfusion, which is found at the early stages of the three dementias reviewed here, will reduce oxygen delivery and lower oxidative phosphorylation promoting a steady decline in the synthesis of the cell energy fuel adenosine triphosphate (ATP)...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28211486/motor-phenotype-is-not-associated-with-vascular-dysfunction-in-symptomatic-huntington-s-disease-transgenic-r6-2-160-cag-mice
#5
A Di Pardo, A Carrizzo, A Damato, S Castaldo, E Amico, L Capocci, M Ambrosio, F Pompeo, C De Sanctis, C C Spinelli, A A Puca, P Remondelli, V Maglione, C Vecchione
Whereas Huntington's disease (HD) is unequivocally a neurological disorder, a critical mass of emerging studies highlights the occurrence of peripheral pathology like cardiovascular defects in both animal models and humans. The overt impairment in cardiac function is normally expected to be associated with peripheral vascular dysfunction, however whether this assumption is reasonable or not in HD is still unknown. In this study we functionally characterized the vascular system in R6/2 mouse model (line 160 CAG), which recapitulates several features of human pathology including cardiac disease...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211292/clinical-and-functional-outcome-of-open-primary-repair-of-triangular-fibrocartilage-complex-tears-associated-with-distal-radius-fractures
#6
Faisal Johandi, Sreedharan Sechachalam
PURPOSE: We evaluate the clinical and functional outcome of open primary repair of acute TFCC tears in distal radius fracture, when there is gross intraoperative distal radioulnar joint (DRUJ) instability after fixation of the distal radius, in the absence of an ulnar styloid fracture or when the ulnar fracture fragment is too small to be fixed. METHODS: A retrospective review of our institution's distal radius fracture database over a 4-year period (January 2010 to December 2013)...
January 2017: Journal of Orthopaedic Surgery
https://www.readbyqxmd.com/read/28210955/the-effects-of-igf-1-on-tnf-%C3%AE-treated-drg-neurons-by-modulating-atf3-and-gap-43-expression-via-pi3k-akt-s6k-signaling-pathway
#7
Lei Zhang, Yaping Yue, Meishuo Ouyang, Huaxiang Liu, Zhenzhong Li
Upregulation of the pro-inflammatory cytokine tumor necrosis factor α (TNF-α) is involved in the development and progression of numerous neurological disorders. Recent reports have challenged the concept that TNF-α exhibits only deleterious effects of pro-inflammatory destruction, and have raised the awareness that it may play a beneficial role in neuronal growth and function in particular conditions, which prompts us to further investigate the role of this cytokine. Insulin-like growth factor-1 (IGF-1) is a cytokine possessing powerful neuroprotective effects in promoting neuronal survival, neuronal differentiation, neurite elongation, and neurite regeneration...
February 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28210902/deletion-of-mammalian-sterile-20-like-kinase-1-attenuates-neuronal-loss-and-improves-locomotor-function-in-a-mouse-model-of-spinal-cord-trauma
#8
Pan-Feng Wang, Da-Yuan Xu, Yuntong Zhang, Xiao-Bin Liu, Yan Xia, Pan-Yu Zhou, Qing-Ge Fu, Shuo-Gui Xu
Neuronal cell death following spinal cord injury (SCI) is an important contributor to neurological deficits. The purpose of our work was to delineate the function of mammalian sterile 20-like kinase 1 (Mst1), a pro-apoptotic kinase and key mediator of apoptotic signaling, in the pathogenesis of an experimental mouse model of SCI. Male mice received a mid-thoracic spinal contusion injury, and it was found that phosphorylation of Mst1 at the injured site was enhanced significantly following SCI. Furthermore, when compared to the wild-type controls, Mst1-deficient mice displayed improved locomotor function by increased Basso mouse scale score...
February 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28210209/lactate-shuttles-in-neuroenergetics-homeostasis-allostasis-and-beyond
#9
REVIEW
Shayne Mason
Understanding brain energy metabolism-neuroenergetics-is becoming increasingly important as it can be identified repeatedly as the source of neurological perturbations. Within the scientific community we are seeing a shift in paradigms from the traditional neurocentric view to that of a more dynamic, integrated one where astrocytes are no longer considered as being just supportive, and activated microglia have a profound influence. Lactate is emerging as the "good guy," contrasting its classical "bad guy" position in the now superseded medical literature...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28210205/the-atp-gated-p2x7-receptor-as-a-target-for-the-treatment-of-drug-resistant-epilepsy
#10
REVIEW
Edward Beamer, Wolfgang Fischer, Tobias Engel
Despite the progress made in the development of new antiepileptic drugs (AEDs), the biggest challenges that epilepsy presents to drug development have remained unchanged for the last 80 years: finding a treatment with potential for modifying disease progression and reducing the percentage of patients resistant to all pharmacological interventions. The mechanism of action of the majority of AEDs is based on blocking Na(+) and/or Ca(2+) channels, promotion of GABA or inhibition of glutamate signaling. In order for further progress to be made, however, a fuller picture of epilepsy will need to be considered, including changes to blood-brain barrier permeability, synaptic plasticity, network reorganization, and gliosis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28209774/methyl-donor-supplementation-alters-cognitive-performance-and-motivation-in-female-offspring-from-high-fat-diet-fed-dams
#11
Sarah E McKee, Nicola M Grissom, Christopher T Herdt, Teresa M Reyes
During gestation, fetal nutrition is entirely dependent on maternal diet. Maternal consumption of excess fat during pregnancy has been linked to an increased risk of neurologic disorders in offspring, including attention deficit/hyperactivity disorder, autism, and schizophrenia. In a mouse model, high-fat diet (HFD)-fed offspring have cognitive and executive function deficits as well as whole-genome DNA and promoter-specific hypomethylation in multiple brain regions. Dietary methyl donor supplementation during pregnancy or adulthood has been used to alter DNA methylation and behavior...
February 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28208696/valproate-attenuates-endoplasmic-reticulum-stress-induced-apoptosis-in-sh-sy5y-cells-via-the-akt-gsk3%C3%AE-signaling-pathway
#12
Zhengmao Li, Fenzan Wu, Xie Zhang, Yi Chai, Daqing Chen, Yuetao Yang, Kebin Xu, Jiayu Yin, Rui Li, Hongxue Shi, Zhouguang Wang, Xiaokun Li, Jian Xiao, Hongyu Zhang
Endoplasmic reticulum (ER) stress-induced apoptosis plays an important role in a range of neurological disorders, such as neurodegenerative diseases, spinal cord injury, and diabetic neuropathy. Valproate (VPA), a typical antiepileptic drug, is commonly used in the treatment of bipolar disorder and epilepsy. Recently, VPA has been reported to exert neurotrophic effects and promote neurite outgrowth, but its molecular mechanism is still unclear. In the present study, we investigated whether VPA inhibited ER stress and promoted neuroprotection and neuronal restoration in SH-SY5Y cells and in primary rat cortical neurons, respectively, upon exposure to thapsigargin (TG)...
February 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208200/massive-pulmonary-embolism-extracorporeal-membrane-oxygenation-and-surgical-pulmonary-embolectomy
#13
Aaron Weinberg, Victor F Tapson, Danny Ramzy
Massive pulmonary embolism (PE) refers to large emboli that cause hemodynamic instability, right ventricular failure, and circulatory collapse. According to the 2016 ACCP Antithrombotic Guidelines, therapy for massive PE should include systemic thrombolytic therapy in conjunction with anticoagulation and supportive care. However, in patients with a contraindication to systemic thrombolytics or in those who fail the above interventions, extracorporeal membrane oxygenation (ECMO) and/or surgical embolectomy may be used to improve oxygenation, achieve hemodynamic stability, and successfully treat massive PE...
February 2017: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28208060/rna-toxicity-and-foci-formation-in-microsatellite-expansion-diseases
#14
REVIEW
Nan Zhang, Tetsuo Ashizawa
More than 30 incurable neurological and neuromuscular diseases are caused by simple microsatellite expansions consisted of 3-6 nucleotides. These repeats can occur in non-coding regions and often result in a dominantly inherited disease phenotype that is characteristic of a toxic RNA gain-of-function. The expanded RNA adopts unusual secondary structures, sequesters various RNA binding proteins to form insoluble nuclear foci, and causes cellular defects at a multisystem level. Nuclear foci are dynamic in size, shape and colocalization of RNA binding proteins in different expansion diseases and tissue types...
February 13, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28207801/kidney-dysfunction-and-cerebral-microbleeds-in-neurologically-healthy-adults
#15
Sang Hyuck Kim, Dong Wook Shin, Jae Moon Yun, Ji Eun Lee, Jae-Sung Lim, Be Long Cho, Hyung-Min Kwon, Jin-Ho Park
INTRODUCTION: Cerebral microbleed (CMB) is a potent risk factor for overt cerebrovascular disease. Although some studies indicated the possible role of renal dysfunction as a risk factor of CMB, the findings could not be generalized. This study aimed to investigate the association between renal dysfunction and cerebral microbleed (CMB) in neurologically healthy adults. MATERIALS AND METHODS: A total of 2,518 subjects who underwent brain MRI as part of health screening were involved in the study...
2017: PloS One
https://www.readbyqxmd.com/read/28207276/hydrophobic-nanoparticles-reduce-the-%C3%AE-sheet-content-of-sevi-amyloid-fibrils-and-inhibit-sevi-enhanced-hiv-infectivity
#16
Daniel A Sheik, Jeffrey M Chamberlain, Lauren R Brooks, Melissa L Clark, Young Hun Kim, Geoffray Leriche, Clifford P Kubiak, Stephen Dewhurst, Jerry Yang
Semen-Derived Enhancer of Virus Infection (SEVI) fibrils are naturally abundant amyloid aggregates found in semen that facilitate viral attachment and internalization of HIV in cells, thereby increasing the probability of infection. Mature SEVI fibrils are comprised of aggregated peptides exhibiting high β-sheet secondary structural characteristics. Herein, we show that polymers containing hydrophobic side chains can interact with SEVI and reduce its β-sheet content by ~45% compared to the β-sheet content of SEVI in the presence of polymers with hydrophilic side chains, as estimated by Polarization Modulation-Infrared Reflectance Absorption Spectroscopy Measurements...
February 16, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28207168/design-and-rationale-of-the-ebbinghaus-trial-a-phase-3-double-blind-placebo-controlled-multicenter-study-to-assess-the-effect-of-evolocumab-on-cognitive-function-in-patients-with-clinically-evident-cardiovascular-disease-and-receiving-statin-background-lipid
#17
Robert P Giugliano, Francois Mach, Kenton Zavitz, Christopher Kurtz, Jingjing Schneider, Huei Wang, Anthony Keech, Terje R Pedersen, Marc S Sabatine, Peter S Sever, Narimon Honarpour, Scott M Wasserman, Brian R Ott
Some observational studies raised concern that statins may cause memory impairment, leading to a US Food and Drug Administration warning. Similar questions were raised regarding proprotein convertase subtilisin/kexin-type 9 inhibitors (PCSK9i) and neurocognitive function. No prospectively designed study has evaluated the relationship between long-term PCSK9i use and cognition changes. Patients with prior cardiovascular disease treated with maximally tolerated statin enrolled in FOURIER (the randomized, double-blind, placebo-controlled cardiovascular outcome study of the PCSK9i evolocumab) could participate in this prospective assessment of cognitive function (EBBINGHAUS)...
February 16, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28206829/validity-of-low-contrast-letter-acuity-as-a-visual-performance-outcome-measure-for-multiple-sclerosis
#18
Laura J Balcer, Jenelle Raynowska, Rachel Nolan, Steven L Galetta, Raju Kapoor, Ralph Benedict, Glenn Phillips, Nicholas LaRocca, Lynn Hudson, Richard Rudick
Low-contrast letter acuity (LCLA) has emerged as the leading outcome measure to assess visual disability in multiple sclerosis (MS) research. As visual dysfunction is one of the most common manifestations of MS, sensitive visual outcome measures are important in examining the effect of treatment. Low-contrast acuity captures visual loss not seen in high-contrast visual acuity (HCVA) measurements. These issues are addressed by the MS Outcome Assessments Consortium (MSOAC), including representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28206828/validity-of-the-timed-25-foot-walk-as-an-ambulatory-performance-outcome-measure-for-multiple-sclerosis
#19
Robert W Motl, Jeffrey A Cohen, Ralph Benedict, Glenn Phillips, Nicholas LaRocca, Lynn D Hudson, Richard Rudick
The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with multiple sclerosis (MS). One of the MSOAC goals is acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful in MS...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28206827/validity-of-the-symbol-digit-modalities-test-as-a-cognition-performance-outcome-measure-for-multiple-sclerosis
#20
Ralph Hb Benedict, John DeLuca, Glenn Phillips, Nicholas LaRocca, Lynn D Hudson, Richard Rudick
Cognitive and motor performance measures are commonly employed in multiple sclerosis (MS) research, particularly when the purpose is to determine the efficacy of treatment. The increasing focus of new therapies on slowing progression or reversing neurological disability makes the utilization of sensitive, reproducible, and valid measures essential. Processing speed is a basic elemental cognitive function that likely influences downstream processes such as memory. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS...
February 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
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