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https://www.readbyqxmd.com/read/28028861/creutzfeldt-jakob-disease
#1
REVIEW
Yasushi Iwasaki 岩崎 靖
This review will explore the clinical and pathological findings of the various forms of Creutzfeldt-Jakob disease (CJD). Clinical findings of CJD are characterized by rapidly progressive cognitive dysfunction, diffusion-weighted magnetic resonance imaging (DWI) hyperintensity, myoclonus, periodic sharp-wave complexes on electroencephalogram and akinetic mutism state. Neuropathologic findings of CJD are characterized by spongiform changes in gray matter, gliosis-particularly hypertrophic astrocytosis-neuropil rarefaction, neuron loss and prion protein (PrP) deposition...
December 28, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/27999185/early-and-progressive-deficit-of-neuronal-activity-patterns-in-a-model-of-local-amyloid-pathology-in-mouse-prefrontal-cortex
#2
Fani Koukouli, Marie Rooy, Uwe Maskos
Alzheimer's Disease (AD) is the most common form of dementia. The condition predominantly affects the cerebral cortex and hippocampus and is characterized by the spread of amyloid plaques and neurofibrillary tangles (NFTs). But soluble amyloid-β (Aβ) oligomers have also been identified to accumulate in the brains of AD patients and correlate with cognitive dysfunction more than the extent of plaque deposition. Here, we developed an adeno-associated viral vector expressing the human mutated amyloid precursor protein (AAV-hAPP)...
December 20, 2016: Aging
https://www.readbyqxmd.com/read/27876534/transcranial-magnetic-stimulation-modifies-astrocytosis-cell-density-and-lipopolysaccharide-levels-in-experimental-autoimmune-encephalomyelitis
#3
Francisco J Medina-Fernández, Evelio Luque, Macarena Aguilar-Luque, Eduardo Agüera, Montserrat Feijóo, Fe I García-Maceira, Begoña M Escribano, Álvaro Pascual-Leone, René Drucker-Colín, Isaac Túnez
AIMS: Experimental autoimmune encephalomyelitis (EAE) is considered a valid experimental model for multiple sclerosis, a chronic neuroinflammatory condition of the central nervous system. Additionally, some evidence has shown that some microbial products such as the bacterial lipopolysaccharide could lead to the activation of reactive immune cells, triggering neuroinflammation. Several studies have found that transcranial magnetic stimulation (TMS) may exert a neuroprotective effect. Therefore, we aimed to assess the effect of TMS on the neuroinflammation occurring in EAE...
November 19, 2016: Life Sciences
https://www.readbyqxmd.com/read/27836728/altered-gene-expression-profile-in-a-mouse-model-of-scn8a-encephalopathy
#4
Ryan S Sprissler, Jacy L Wagnon, Rosie K Bunton-Stasyshyn, Miriam H Meisler, Michael F Hammer
SCN8A encephalopathy is a severe, early-onset epilepsy disorder resulting from de novo gain-of-function mutations in the voltage-gated sodium channel Nav1.6. To identify the effects of this disorder on mRNA expression, RNA-seq was performed on brain tissue from a knock-in mouse expressing the patient mutation p.Asn1768Asp (N1768D). RNA was isolated from forebrain, cerebellum, and brainstem both before and after seizure onset, and from age-matched wildtype littermates. Altered transcript profiles were observed only in forebrain and only after seizures...
February 2017: Experimental Neurology
https://www.readbyqxmd.com/read/27834214/motor-neuron-disease-tdp-43-pathology-and-memory-deficits-in-mice-expressing-als-ftd-linked-ubqln2-mutations
#5
Nhat T T Le, Lydia Chang, Irina Kovlyagina, Polymnia Georgiou, Nathaniel Safren, Kerstin E Braunstein, Mark D Kvarta, Adam M Van Dyke, Tara A LeGates, Thomas Philips, Brett M Morrison, Scott M Thompson, Adam C Puche, Todd D Gould, Jeffrey D Rothstein, Philip C Wong, Mervyn J Monteiro
Missense mutations in ubiquilin 2 (UBQLN2) cause ALS with frontotemporal dementia (ALS-FTD). Animal models of ALS are useful for understanding the mechanisms of pathogenesis and for preclinical investigations. However, previous rodent models carrying UBQLN2 mutations failed to manifest any sign of motor neuron disease. Here, we show that lines of mice expressing either the ALS-FTD-linked P497S or P506T UBQLN2 mutations have cognitive deficits, shortened lifespans, and develop motor neuron disease, mimicking the human disease...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27826896/blood-brain-barrier-impairment-in-hiv-positive-na%C3%A3-ve-and-effectively-treated-patients-immune-activation-versus-astrocytosis
#6
A Calcagno, A Romito, C Atzori, V Ghisetti, C Cardellino, S Audagnotto, E Scarvaglieri, F Lipani, D Imperiale, G Di Perri, S Bonora
Blood brain barrier (BBB) damage is a common feature in central nervous system infections by HIV and it may persist despite effective antiretroviral therapy. Astrocyte involvement has not been studied in this setting. Patients were enrolled in an ongoing prospective study and subjects with central nervous system-affecting disorders were excluded. Patients were divided into two groups: treated subjects with cerebrospinal fluid (CSF) HIV RNA <50 copies/mL (CSF-controllers) and in late-presenters CD4+ T lymphocytes <100/uL...
November 8, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/27798188/oxidation-of-kcnb1-potassium-channels-causes-neurotoxicity-and-cognitive-impairment-in-a-mouse-model-of-traumatic-brain-injury
#7
Wei Yu, Randika Parakramaweera, Shavonne Teng, Manasa Gowda, Yashsavi Sharad, Smita Thakker-Varia, Janet Alder, Federico Sesti
: The delayed rectifier potassium (K(+)) channel KCNB1 (Kv2.1), which conducts a major somatodendritic current in cortex and hippocampus, is known to undergo oxidation in the brain, but whether this can cause neurodegeneration and cognitive impairment is not known. Here, we used transgenic mice harboring human KCNB1 wild-type (Tg-WT) or a nonoxidable C73A mutant (Tg-C73A) in cortex and hippocampus to determine whether oxidized KCNB1 channels affect brain function. Animals were subjected to moderate traumatic brain injury (TBI), a condition characterized by extensive oxidative stress...
October 26, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27781299/mesenchymal-stem-cells-attenuate-mri-identifiable-injury-protect-white-matter-and-improve-long-term-functional-outcomes-after-neonatal-focal-stroke-in-rats
#8
Cindy T van Velthoven, Mark Dzietko, Michael F Wendland, Nikita Derugin, Joel Faustino, Cobi J Heijnen, Donna M Ferriero, Zinaida S Vexler
Cell therapy has emerged as a potential treatment for many neurodegenerative diseases including stroke and neonatal ischemic brain injury. Delayed intranasal administration of mesenchymal stem cells (MSCs) after experimental hypoxia-ischemia and after a transient middle cerebral artery occlusion (tMCAO) in neonatal rats has shown improvement in long-term functional outcomes, but the effects of MSCs on white matter injury (WMI) are insufficiently understood. In this study we used longitudinal T2-weighted (T2W) and diffusion tensor magnetic resonance imaging (MRI) to characterize chronic injury after tMCAO induced in postnatal day 10 (P10) rats and examined the effects of delayed MSC administration on WMI, axonal coverage, and long-term somatosensory function...
October 26, 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27773938/high-fat-induces-acute-and-chronic-inflammation-in-the-hypothalamus-effect-of-high-fat-diet-palmitate-and-tnf-%C3%AE-on-appetite-regulating-npy-neurons
#9
P S Dalvi, J A Chalmers, V Luo, D-Yd Han, L Wellhauser, Y Liu, D Q Tran, J Castel, S Luquet, M B Wheeler, D D Belsham
BACKGROUND: Consumption of dietary fat is one of the key factors leading to obesity. High-fat diet (HFD)-induced obesity is characterized by induction of inflammation in the hypothalamus; however, the temporal regulation of proinflammatory markers and their impact on hypothalamic appetite-regulating neuropeptide Y/agouti-related peptide (NPY/AgRP) neurons remains undefined. METHODS: Mice were injected with an acute lipid infusion for 24 h or fed a HFD over 8-20 weeks...
January 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27743984/non-viral-xylosyltransferase-1-sirna-delivery-as-an-effective-alternative-to-chondroitinase-in-an-in-vitro-model-of-reactive-astrocytes
#10
Mohammad T Abu-Rub, Ben Newland, Michelle Naughton, Wenxin Wang, Siobhan McMahon, Abhay Pandit
Reactive astrocytosis and the subsequent glial scar is ubiquitous to injuries of the central nervous system, especially spinal cord injury (SCI) and primarily serves to protect against further damage, but is also a prominent inhibitor of regeneration. Manipulating the glial scar by targeting chondroitin sulfate proteoglycans (CSPGs) has been the focus of much study as a means to improve axon regeneration and subsequently functional recovery. In this study we investigate the ability of small interfering RNA (siRNA) delivered by a non-viral polymer vector to silence the rate-limiting enzyme involved in CSPG synthesis...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27639427/propagation-of-damage-in-the-rat-brain-following-sarin-exposure-differential-progression-of-early-processes
#11
Shlomi Lazar, Inbal Egoz, Rachel Brandeis, Shira Chapman, Eugenia Bloch-Shilderman, Ettie Grauer
Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6h post exposure while TSPO receptor density increased only at 24h...
November 1, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27633250/positron-emission-tomography-measurement-of-brain-mao-b-inhibition-in-patients-with-alzheimer-s-disease-and-elderly-controls-after-oral-administration-of-sembragiline
#12
Stefan Sturm, Anton Forsberg, Stephane Nave, Per Stenkrona, Nicholas Seneca, Andrea Varrone, Robert A Comley, Patrik Fazio, Candice Jamois, Ryuji Nakao, Zbigniew Ejduk, Nabil Al-Tawil, Ulrika Akenine, Christer Halldin, Niels Andreasen, Benedicte Ricci
PURPOSE: In Alzheimer's disease (AD), increased metabolism of monoamines by monoamine oxidase type B (MAO-B) leads to the production of toxic reactive oxygen species (ROS), which are thought to contribute to disease pathogenesis. Inhibition of the MAO-B enzyme may restore brain levels of monoaminergic neurotransmitters, reduce the formation of toxic ROS and reduce neuroinflammation (reactive astrocytosis), potentially leading to neuroprotection. Sembragiline (also referred as RO4602522, RG1577 and EVT 302 in previous communications) is a potent, selective and reversible inhibitor of MAO-B developed as a potential treatment for AD...
September 16, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27609520/hiv-1-tat-induces-unfolded-protein-response-and-endoplasmic-reticulum-stress-in-astrocytes-and-causes-neurotoxicity-through-glial-fibrillary-acidic-protein-gfap-activation-and-aggregation
#13
Yan Fan, Johnny J He
HIV-1 Tat is a major culprit for HIV/neuroAIDS. One of the consistent hallmarks of HIV/neuroAIDS is reactive astrocytes or astrocytosis, characterized by increased cytoplasmic accumulation of the intermediate filament glial fibrillary acidic protein (GFAP). We have shown that that Tat induces GFAP expression in astrocytes and that GFAP activation is indispensable for astrocyte-mediated Tat neurotoxicity. However, the underlying molecular mechanisms are not known. In this study, we showed that Tat expression or GFAP expression led to formation of GFAP aggregates and induction of unfolded protein response (UPR) and endoplasmic reticulum (ER) stress in astrocytes...
October 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27609518/hiv-1-tat-promotes-lysosomal-exocytosis-in-astrocytes-and-contributes-to-astrocyte-mediated-tat-neurotoxicity
#14
Yan Fan, Johnny J He
Tat interaction with astrocytes has been shown to be important for Tat neurotoxicity and HIV/neuroAIDS. We have recently shown that Tat expression leads to increased glial fibrillary acidic protein (GFAP) expression and aggregation and activation of unfolded protein response/endoplasmic reticulum (ER) stress in astrocytes and causes neurotoxicity. However, the exact molecular mechanism of astrocyte-mediated Tat neurotoxicity is not defined. In this study, we showed that neurotoxic factors other than Tat protein itself were present in the supernatant of Tat-expressing astrocytes...
October 21, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27601660/infiltrating-monocytes-promote-brain-inflammation-and-exacerbate-neuronal-damage-after-status-epilepticus
#15
Nicholas H Varvel, Jonas J Neher, Andrea Bosch, Wenyi Wang, Richard M Ransohoff, Richard J Miller, Raymond Dingledine
The generalized seizures of status epilepticus (SE) trigger a series of molecular and cellular events that produce cognitive deficits and can culminate in the development of epilepsy. Known early events include opening of the blood-brain barrier (BBB) and astrocytosis accompanied by activation of brain microglia. Whereas circulating monocytes do not infiltrate the healthy CNS, monocytes can enter the brain in response to injury and contribute to the immune response. We examined the cellular components of innate immune inflammation in the days following SE by discriminating microglia vs...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27586142/nkcc1-up-regulation-contributes-to-early-post-traumatic-seizures-and-increased-post-traumatic-seizure-susceptibility
#16
Fushun Wang, Xiaowei Wang, Lee A Shapiro, Maria L Cotrina, Weimin Liu, Ernest W Wang, Simeng Gu, Wei Wang, Xiaosheng He, Maiken Nedergaard, Jason H Huang
Traumatic brain injury (TBI) is not only a leading cause for morbidity and mortality in young adults (Bruns and Hauser, Epilepsia 44(Suppl 10):210, 2003), but also a leading cause of seizures. Understanding the seizure-inducing mechanisms of TBI is of the utmost importance, because these seizures are often resistant to traditional first- and second-line anti-seizure treatments. The early post-traumatic seizures, in turn, are a contributing factor to ongoing neuropathology, and it is critically important to control these seizures...
September 1, 2016: Brain Structure & Function
https://www.readbyqxmd.com/read/27513991/calpain-inhibition-reduces-structural-and-functional-impairment-of-retinal-ganglion-cells-in-experimental-optic-neuritis
#17
Amena W Smith, Baerbel Rohrer, Lee Wheless, Supriti Samantaray, Swapan K Ray, Jun Inoue, Mitsuyoshi Azuma, Naren L Banik
Optic neuritis (ON), inflammation of the optic nerve, is strongly associated with multiple sclerosis. ON pathology is characterized by attack of autoreactive T cells against optic nerve antigens, resulting in demyelination, death of retinal ganglion cells, and cumulative visual impairment. A model of experimental autoimmune encephalomyelitis (EAE) was utilized to study the onset and progression of ON and the neuroprotective efficacy of oral treatment with the calpain inhibitor SNJ 1945. EAE was actively induced in B10...
October 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27469356/epileptic-activity-increases-cerebral-amino-acid-transport-assessed-by-18f-fluoroethyl-l-tyrosine-amino-acid-pet-a-potential-brain-tumor-mimic
#18
Markus Hutterer, Yvonne Ebner, Markus J Riemenschneider, Antje Willuweit, Mark McCoy, Barbara Egger, Michael Schröder, Christina Wendl, Dirk Hellwig, Jirka Grosse, Karin Menhart, Martin Proescholdt, Brita Fritsch, Horst Urbach, Guenther Stockhammer, Ulrich Roelcke, Norbert Galldiks, Philipp T Meyer, Karl-Josef Langen, Peter Hau, Eugen Trinka
: O-(2-(18)F-fluoroethyl)-l-tyrosine ((18)F-FET) PET is a well-established method increasingly used for diagnosis, treatment planning, and monitoring in gliomas. Epileptic activity, frequently occurring in glioma patients, can influence MRI findings. Whether seizures also affect (18)F-FET PET imaging is currently unknown. The aim of this retrospective analysis was to investigate the brain amino acid metabolism during epileptic seizures by (18)F-FET PET and to elucidate the pathophysiologic background...
January 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27468040/hydrocephalus-in-three-juvenile-north-american-black-bears-ursus-americanus
#19
Sylvia H Ferguson, Janelle Novak, Silke Hecht, Linden E Craig
Hydrocephalus has been reported in a variety of species, including the North American black bear ( Ursus americanus ). This report describes three cases of hydrocephalus in this species from wild bears aged 3-4 mo considered retrospectively from necropsy records of one institution. Clinical signs included cortical blindness and ataxia. Primary gross findings were doming of the skull, gyri compression and flattening, and lateral ventricle dilation. Two cases had severe bilateral ventricular dilation with loss of the septum pellucidum; atrophy of the surrounding corpus callosum; and bilateral periventricular tears involving the caudate nuclei, internal capsule, and adjacent cerebrum...
June 2016: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/27436355/an-autopsied-case-of-mm1%C3%A2-%C3%A2-mm2-cortical-with-thalamic-type-sporadic-creutzfeldt-jakob-disease-presenting-with-hyperintensities-on-diffusion-weighted-mri-before-clinical-onset
#20
Yasushi Iwasaki, Keiko Mori, Masumi Ito, Maya Mimuro, Tetsuyuki Kitamoto, Mari Yoshida
A 78-year-old Japanese man presented with rapidly progressive dementia and gait disturbances. Eight months before the onset of clinical symptoms, diffusion-weighted magnetic resonance imaging (DWI) demonstrated hyperintensities in the right temporal, right parietal and left medial occipital cortices. Two weeks after symptom onset, DWI showed extensive hyperintensity in the bilateral cerebral cortex, with regions of higher brightness that existed prior to symptom onset still present. Four weeks after clinical onset, periodic sharp wave complexes were identified on an electroencephalogram...
July 20, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
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