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https://www.readbyqxmd.com/read/28431433/experimental-anterior-ischemic-optic-neuropathy-in-diabetic-mice-exhibited-severe-retinal-swelling-associated-with-vegf-elevation
#1
Ming-Hui Sun, Mohammad Ali Shariati, Yaping Joyce Liao
Purpose: Diabetes mellitus (DM) is one of the most important risk factors for nonarteritic anterior ischemic optic neuropathy (AION). In this study, we investigated for the first time the impact of experimental AION in a DM model. Methods: We induced a photochemical thrombosis model of AION after streptozotocin-induced DM and performed serial optical coherence tomography (OCT), morphometric analyses, and VEGF levels in the retina and sera. Results: Compared with non-DM animals, experimental AION in DM mice led to significantly greater retinal swelling on day 1 and worse thinning at week 3 on OCT measurements...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28431428/computational-and-in-vitro-experimental-investigation-of-intrathecal-drug-distribution-parametric-study-of-the-effect-of-injection-volume-cerebrospinal-fluid-pulsatility-and-drug-uptake
#2
Kevin M Tangen, Roxanne Leval, Ankit I Mehta, Andreas A Linninger
BACKGROUND: Intrathecal drug delivery is an attractive option to circumvent the blood-brain barrier for pain management through its increased efficacy of pain relief, reduction in adverse side effects, and cost-effectiveness. Unfortunately, there are limited guidelines for physicians to choose infusion or drug pump settings to administer therapeutic doses to specific regions of the spine or the brain. Although empiric trialing of intrathecal drugs is critical to determine the sustained side effects, currently there is no inexpensive in vitro method to guide the selection of spinal drug delivery parameters...
May 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28431402/micrometastasis-of-endometriosis-to-distant-organs-in-a-murine-model
#3
Elham N Samani, Ramanaiah Mamillapalli, Fei Li, Levent Mutlu, Demetra Hufnagel, Graciela Krikun, Hugh S Taylor
Endometriosis is an inflammatory gynecological disorder among reproductive-aged women caused by the engraftment and proliferation of endometrial cells outside the uterus, most commonly in the pelvis. It is thought that the disease arises primarily from retrograde menstruation where cells from the endometrium travel through the fallopian tubes to the peritoneal cavity. However, migration of endometriosis-derived cells to distant organs outside of the peritoneal cavity have not been explored. In the present study, we developed and validated a mouse model of disseminated endometriosis using syngeneic DsRed endometrial tissue introduced into the peritoneum of immunocompetent mice...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431369/the-temporal-paradox-of-hebbian-learning-and-homeostatic-plasticity
#4
REVIEW
Friedemann Zenke, Wulfram Gerstner, Surya Ganguli
Hebbian plasticity, a synaptic mechanism which detects and amplifies co-activity between neurons, is considered a key ingredient underlying learning and memory in the brain. However, Hebbian plasticity alone is unstable, leading to runaway neuronal activity, and therefore requires stabilization by additional compensatory processes. Traditionally, a diversity of homeostatic plasticity phenomena found in neural circuits is thought to play this role. However, recent modelling work suggests that the slow evolution of homeostatic plasticity, as observed in experiments, is insufficient to prevent instabilities originating from Hebbian plasticity...
April 18, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28431340/first-macrocyclic-3-rd-generation-alk-inhibitor-for-treatment-of-alk-ros1-cancer-clinical-and-designing-strategy-update-of-lorlatinib
#5
REVIEW
Sulman Basit, Zaman Ashraf, Kwangho Lee, Muhammad Latif
Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to 2(nd)-generation ALK inhibitors. Lorlatinib (PF-06463922) (6) is a 3(rd)-generation macrocyclic ALK-TKI that demonstrates many advantages over 2(nd)-generation ALK inhibitors. Lorlatinib has demonstrated decent kinase selectivity, promising pharmacokinetic profile, selective brain-penetration and strong antiproliferative activity in several ALK/ROS1-driven tumor models. The current review describes the activity spectrum, key events from discovery to clinical applications and the evidences that lorlatinib acts as an ALK/ROS1 inhibitor in clinical settings...
April 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431287/age-and-gender-effects-of-11-c-itmm-binding-to-metabotropic-glutamate-receptor-type-1-in-healthy-human-participants
#6
Muneyuki Sakata, Jun Toyohara, Kenji Ishibashi, Kei Wagatsuma, Kenji Ishii, Ming-Rong Zhang, Kiichi Ishiwata
We examined possible age- and gender-related changes in binding of the selective antagonist N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-(11)C-methoxy-N-methylbenzamide ((11)C-ITMM) to metabotropic glutamate receptor type 1 in healthy human brains. Dynamic (11)C-ITMM positron emission tomography scans (90 min) with serial arterial blood sampling were performed in 15 young and 24 older healthy adult volunteers. The total distribution volume (VT) of several brain regions was estimated with 2-tissue compartment model analysis...
March 28, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28430993/a-multi-systemic-mitochondrial-disorder-due-to-a-dominant-p-y955h-disease-variant-in-dna-polymerase-gamma
#7
Triinu Siibak, Paula Clemente, Ana Bratic, Helene Bruhn, Timo E S Kauppila, Bertil Macao, Florian A Schober, Nicole Lesko, Rolf Wibom, Karin Naess, Inger Nennesmo, Anna Wedell, Bradley Peter, Christoph Freyer, Maria Falkenberg, Anna Wredenberg
Mutations in the mitochondrial DNA polymerase, POLG, are associated with a variety of clinical presentations, ranging from early onset fatal brain disease in Alpers syndrome to chronic progressive external ophthalmoplegia. The majority of mutations are linked with disturbances of mitochondrial DNA (mtDNA) integrity and maintenance. On a molecular level, depending on their location within the enzyme, mutations either lead to mtDNA depletion or the accumulation of multiple mtDNA deletions, and in some cases these molecular changes can be correlated to the clinical presentation...
April 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28430990/three-dimensional-dose-prediction-and-validation-with-the-radiobiological-gamma-index-based-on-a-relative-seriality-model-for-head-and-neck-imrt
#8
Noriaki Hamatani, Iori Sumida, Yutaka Takahashi, Michio Oda, Yuji Seo, Fumiaki Isohashi, Keisuke Tamari, Kazuhiko Ogawa
This study proposes a quality assurance (QA) method incorporating radiobiological factors based on the QUANTEC-determined tumor control probability and the normal tissue complication probability (NTCP) of head-and-neck intensity-modulated radiation therapy (HN-IMRT). Per-beam measurements were conducted for 20 cases using a 2D detector array. Three-dimensional predicted dose distributions within targets and organs at risk were reconstructed based on the per-beam QA results derived from differences between planned and measured doses...
April 19, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28430981/central-nervous-system-glp-1-receptors-regulate-islet-hormone-secretion-and-glucose-homeostasis-in-male-rats
#9
Lene Jessen, Eric P Smith, Yvonne Ulrich-Lai, James P Herman, Randy J Seeley, Darleen Sandoval, David D'Alessio
The glucagon-like peptide 1 (GLP-1) system plays an important role in blood glucose regulation, in great part through coordinate control of insulin and glucagon secretion. These effects are generally attributed to GLP-1 produced in peripheral sites, principally the intestine. GLP-1 is also produced in hindbrain neurons that signal through GLP-1 receptors (GLP-1r) expressed in brain regions involved in metabolic regulation. GLP-1 in the central nervous system (CNS) induces satiety, visceral illness, and stress responses...
April 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28430857/repurposed-drugs-targeting-eif2%C3%AE-p-mediated-translational-repression-prevent-neurodegeneration-in-mice
#10
Mark Halliday, Helois Radford, Karlijn A M Zents, Collin Molloy, Julie A Moreno, Nicholas C Verity, Ewan Smith, Catharine A Ortori, David A Barrett, Martin Bushell, Giovanna R Mallucci
Signalling through the PERK/eIF2α-P branch of the unfolded protein response plays a critical role in controlling protein synthesis rates in cells. This pathway is overactivated in brains of patients with Alzheimer's disease and related disorders and has recently emerged as a promising therapeutic target for these currently untreatable conditions. Thus, in mouse models of neurodegenerative disease, prolonged overactivation of PERK/eIF2α-P signalling causes sustained attenuation of protein synthesis, leading to memory impairment and neuronal loss...
April 19, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28430607/simulated-weightlessness-affects-the-expression-and-activity-of-neuronal-nitric-oxide-synthase-in-the-rat-brain
#11
Nara Yoon, Kiyong Na, Hyun-Soo Kim
Spaceflight induces pathophysiological alterations in various organs. To study pathophysiological adaptations to weightlessness on the ground, the tail suspension (TS) rat model has been used to simulate the effects of weightlessness. There is currently little information on the effect of TS on the expression and activity of nitric oxide synthase (NOS) in the brain. In this study, we examined time-dependent alterations in the expression and activity of neuronal NOS (nNOS) in the brains of TS rats. Male Sprague-Dawley rats were tail-suspended for 1 (TS1), 7 (TS7), and 14 (TS14) days or rested on the ground for 3 days after 14 days of TS...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430533/new-directions-in-the-rational-design-of-electrical-and-magnetic-seizure-therapies-individualized-low-amplitude-seizure-therapy-ilast-and-magnetic-seizure-therapy-mst
#12
Thomas Radman, Sarah H Lisanby
Electroconvulsive therapy remains a key treatment option for severe cases of depression, but undesirable side-effects continue to limit its use. Innovations in the design of novel seizure therapies seek to improve its risk benefit ratio through enhanced control of the focality of stimulation. The design of seizure therapies with increased spatial precision is motivated by avoiding stimulation of deep brain structures implicated in memory retention, including the hippocampus. The development of two innovations in seizure therapy-individualized low-amplitude seizure therapy (iLAST) and magnetic seizure therapy (MST), are detailed...
April 21, 2017: International Review of Psychiatry
https://www.readbyqxmd.com/read/28430368/proteomic-data-in-morphine-addiction-versus-real-protein-activity-metabolic-enzymes
#13
Anna Antolak, Anna Bodzoń-Kułakowska, Ewa Cetnarska, Monika Pietruszka, Marta Marszałek-Grabska, Jolanta Kotlińska, Piotr Suder
Drug dependence is an escalating problem worldwide and many efforts are being made to understand the molecular basis of addiction. The morphine model is widely used in these investigations. To date, at least 29 studies exploring the influence of morphine on mammals' proteomes have been published. Among various proteins indicated as up- or down-regulated, the expression changes of enzymes engaged in energy metabolism pathways have often been confirmed. To verify whether proteomics-indicated alterations in enzyme levels reflect changes in their activity, four enzymes: PK, MDH, Complex I, and Complex V were investigated in morphine addiction and abstinence models...
April 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28430363/cerebrolysin-for-acute-ischaemic-stroke
#14
REVIEW
Liliya Eugenevna Ziganshina, Tatyana Abakumova, Ludivine Vernay
BACKGROUND: Cerebrolysin is a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue, which has potential neuroprotective and neurotrophic properties. It is widely used in the treatment of acute ischaemic stroke in Russia, Eastern Europe, China, and other Asian and post-Soviet countries. OBJECTIVES: To assess the benefits and risks of cerebrolysin for treating acute ischaemic stroke. SEARCH METHODS: In May 2016 we searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase, Web of Science Core Collection, with Science Citation Index, LILACS, OpenGrey, and a number of Russian Databases...
April 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28430292/failure-of-the-vascular-hypothesis-of-multiple-sclerosis-in-a-rat-model-of-chronic-cerebrospinal-venous-insufficiency
#15
Maha M A Zakaria, Shahira Y Mikhael, Azza K Abu Hussein, Rania A Salah El-Din, Hany W Abd El-Malak, Iman H Hewedi, Hany S Nadim
<i>Chronic cerebrospinal venous insufficiency (CCSVI) is a series of stenotic malformations in the cerebrospinal venous outflow routes, which is postulated to cause multiple sclerosis (MS). The hypotheses assumed that CCSVI leads to iron deposition which triggers inflammation and demyelination in MS. Invasive endovascular treatment of CCSVI was initiated based on the previous theory. The present study was designed to validate this hypothesis using a rat model of CCSVI. Bilateral jugular vein ligation (JVL) was performed on female albino rats (n = 15), and sham-operated rats (n = 15) were used as a control group...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28430040/foraging-value-risk-avoidance-and-multiple-control-signals-how-the-acc-controls-value-based-decision-making
#16
Joshua W Brown, William H Alexander
Recent work on the role of the ACC in cognition has focused on choice difficulty, action value, risk avoidance, conflict resolution, and the value of exerting control among other factors. A main underlying question is what are the output signals of ACC, and relatedly, what is their effect on downstream cognitive processes? Here we propose a model of how ACC influences cognitive processing in other brain regions that choose actions. The model builds on the earlier Predicted Response Outcome model and suggests that ACC learns to represent specifically the states in which the potential costs or risks of an action are high, on both short and long timescales...
April 21, 2017: Journal of Cognitive Neuroscience
https://www.readbyqxmd.com/read/28429775/fucoxanthin-provides-neuroprotection-in-models-of-traumatic-brain-injury-via-the-nrf2-are-and-nrf2-autophagy-pathways
#17
Li Zhang, Handong Wang, Youwu Fan, Yongyue Gao, Xiang Li, Zhigang Hu, Ke Ding, Yujie Wang, Xiaoliang Wang
Fucoxanthin is abundant in seaweed and is considered as a powerful antioxidant. It has been proposed to possess anti-cancer, anti-obesity and anti-diabetes effects. However, its roles in brain injury models have not been fully understood. The objective of this study was to investigate the neuroprotection of fucoxanthin in models of traumatic brain injury (TBI) and the role of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant-response element (ARE) and Nrf2-autophagy pathways in the putative neuroprotection...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429734/neuroprotective-pentapeptide-cn-105-is-associated-with-reduced-sterile-inflammation-and-improved-functional-outcomes-in-a-traumatic-brain-injury-murine-model
#18
Daniel T Laskowitz, Haichen Wang, Tony Chen, David T Lubkin, Viviana Cantillana, Tian Ming Tu, Dawn Kernagis, Guanen Zhou, Gary Macy, Bradley J Kolls, Hana N Dawson
At present, there are no proven pharmacological treatments demonstrated to improve long term functional outcomes following traumatic brain injury(TBI). In the setting of non-penetrating TBI, sterile brain inflammatory responses are associated with the development of cerebral edema, intracranial hypertension, and secondary neuronal injury. There is increasing evidence that endogenous apolipoprotein E(apoE) modifies the neuroinflammatory response through its role in downregulating glial activation, however, the intact apoE holoprotein does not cross the blood-brain barrier due to its size...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429729/weak-connections-form-an-infinite-number-of-patterns-in-the-brain
#19
Hai-Peng Ren, Chao Bai, Murilo S Baptista, Celso Grebogi
Recently, much attention has been paid to interpreting the mechanisms for memory formation in terms of brain connectivity and dynamics. Within the plethora of collective states a complex network can exhibit, we show that the phenomenon of Collective Almost Synchronisation (CAS), which describes a state with an infinite number of patterns emerging in complex networks for weak coupling strengths, deserves special attention. We show that a simulated neuron network with neurons weakly connected does produce CAS patterns, and additionally produces an output that optimally model experimental electroencephalograph (EEG) signals...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429535/a-cross-circulated-bicephalic-model-of-head-transplantation
#20
Peng-Wei Li, Xin Zhao, Yun-Long Zhao, Bing-Jian Wang, Yang Song, Zi-Long Shen, Hong-Jun Jiang, Hai Jin, Sergio Canavero, Xiao-Ping Ren
AIMS: A successful cephalosomatic anastomosis ("head transplant") requires, among others, the ability to control long-term immune rejection and avoidance of ischemic events during the head transference phase. We developed a bicephalic model of head transplantation to study these aspects. METHODS AND RESULTS: The thoracic aorta and superior vena cava of a donor rat were anastomosed with the carotid artery and extracorporeal veins of a recipient rat by vascular grafts...
April 21, 2017: CNS Neuroscience & Therapeutics
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