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https://www.readbyqxmd.com/read/29146953/achievements-and-obstacles-of-remyelinating-therapies-in-multiple-sclerosis
#1
REVIEW
Martin Stangel, Tanja Kuhlmann, Paul M Matthews, Trevor J Kilpatrick
Remyelination in the CNS is the natural process of damage repair in demyelinating diseases such as multiple sclerosis (MS). However, remyelination becomes inadequate in many people with MS, which results in axonal degeneration and clinical disability. Enhancement of remyelination is a logical therapeutic goal; nevertheless, all currently licensed therapies for MS are immunomodulatory and do not support remyelination directly. Several molecular pathways have been identified as potential therapeutic targets to induce remyelination, and some of these have now been assessed in proof-of-concept clinical trials...
November 17, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/29140736/extremely-low-frequency-magnetic-field-protects-injured-spinal-cord-from-the-microglia-and-iron-induced-tissue-damage
#2
Soumil Dey, Samrat Bose, Suneel Kumar, Ravinder Rathore, Rashmi Mathur, Suman Jain
Spinal cord injury (SCI) is insult to the spinal cord, which results in loss of sensory and motor function below the level of injury. SCI results in both immediate mechanical damage and secondary tissue degeneration. Following traumatic insult, activated microglia release proinflammatory cytokines and excess iron due to hemorrhage, initiating oxidative stress that contributes to secondary degeneration. Literature suggests that benefits are visible with the reduction in concentration of iron and activated microglia in SCI...
November 15, 2017: Electromagnetic Biology and Medicine
https://www.readbyqxmd.com/read/29138314/imaging-and-quantifying-ganglion-cells-and-other-transparent-neurons-in-the-living-human-retina
#3
Zhuolin Liu, Kazuhiro Kurokawa, Furu Zhang, John J Lee, Donald T Miller
Ganglion cells (GCs) are fundamental to retinal neural circuitry, processing photoreceptor signals for transmission to the brain via their axons. However, much remains unknown about their role in vision and their vulnerability to disease leading to blindness. A major bottleneck has been our inability to observe GCs and their degeneration in the living human eye. Despite two decades of development of optical technologies to image cells in the living human retina, GCs remain elusive due to their high optical translucency...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29130658/-vein-nerve-conduit-supported-by-vascular-stent-in-the-regeneration-of-peripheral-nerve-in-rabbits
#4
Wei-Kun Meng, Zhong Huang, Zhen Tan, Liang Li, Qiang Guo, Zhen Zhang, Cheng-Xi Wu, Lei Liu, Fu-Guo Huang, Guang-Lin Wang
OBJECTIVE: To evaluate the effectiveness of autologous vein nerve conduit supported by vascular stent in repairing a 10 mm gap peroneal nerve in white New Zealand rabbits. METHODS: 30 New Zealand rabbits were randomly divided into three groups: autologous nerve group (group A),conventional autologous vein nerve conduit group (group B),autologous vein nerve conduit supported by vascular stent group (group C). 10 mm common peroneal nerve was cut off. In groups A,the peroneal nerve was turned 180 ° before suturing...
September 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/29123469/suppression-of-inflammatory-demyelinaton-and-axon-degeneration-through-inhibiting-kv3-channels
#5
Peter Jukkola, Yuanzheng Gu, Amy E Lovett-Racke, Chen Gu
The development of neuroprotective and repair strategies for treating progressive multiple sclerosis (MS) requires new insights into axonal injury. 4-aminopyridine (4-AP), a blocker of voltage-gated K(+) (Kv) channels, is used in symptomatic treatment of progressive MS, but the underlying mechanism remains unclear. Here we report that deleting Kv3.1-the channel with the highest 4-AP sensitivity-reduces clinical signs in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. In Kv3.1 knockout (KO) mice, EAE lesions in sensory and motor tracts of spinal cord were markedly reduced, and radial astroglia were activated with increased expression of brain derived neurotrophic factor (BDNF)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29123152/neural-specific-deletion-of-mitochondrial-p32-c1qbp-leads-to-leukoencephalopathy-due-to-undifferentiated-oligodendrocyte-and-axon-degeneration
#6
Mikako Yagi, Takeshi Uchiumi, Noriaki Sagata, Daiki Setoyama, Rie Amamoto, Yuichi Matsushima, Dongchon Kang
Mitochondrial dysfunction is a critical step in the pathogenesis of many neurodegenerative diseases. The p32/ C1qbp gene functions as an essential RNA and protein chaperone in mitochondrial translation, and is indispensable for embryonic development. However, little is known about the consequences of mitochondrial dysfunction of p32 deletion in the brain development. Here, we found that mice lacking p32 in the central nervous system (p32cKO mice) showed white matter degeneration accompanied by progressive oligodendrocyte loss, axon degeneration and vacuolation in the mid brain and brain stem regions...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29121969/microglial-dynamics-after-axotomy-induced-retinal-ganglion-cell-death
#7
Francisco M Nadal-Nicolás, Manuel Jiménez-López, Manuel Salinas-Navarro, Paloma Sobrado-Calvo, Manuel Vidal-Sanz, Marta Agudo-Barriuso
BACKGROUND: Microglial cells (MCs) are the sentries of the central nervous system. In health, they are known as surveying MCs because they examine the tissue to maintain the homeostasis. In disease, they activate and, among other functions, become phagocytic to clean the cellular debris. In this work, we have studied the behavior of rat retinal MCs in two models of unilateral complete intraorbital optic nerve axotomy which elicit a different time course of retinal ganglion cell (RGC) loss...
November 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29120410/molecular-analysis-of-axonal-intrinsic-and-glial-associated-co-regulation-of-axon-degeneration
#8
Alejandra Catenaccio, Maica Llavero Hurtado, Paula Diaz, Douglas J Lamont, Thomas M Wishart, Felipe A Court
Wallerian degeneration is an active program tightly associated with axonal degeneration, required for axonal regeneration and functional recovery after nerve damage. Here we provide a functional molecular foundation for our undertstanding of the complex non-cell autonomous role of glial cells in the regulation of axonal degeneration. To shed light on the complexity of the molecular machinery governing axonal degeneration we employ a multi-model, unbiased, in vivo approach combining morphological assesment and quantitative proteomics with in silico-based higher order functional clustering to genetically uncouple the intrinsic and extrinsic processes governing Wallerian degeneration...
November 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29119928/rational-basis-for-nutraceuticals-in-the-treatment-of-glaucoma
#9
Morrone Luigi Antonio, Rombola Laura, Adornetto Annagrazia, Corasaniti Maria Tiziana, Russo Rossella
Glaucoma, the second leading cause of blindness worldwide, is a chronic optic neuropathy characterized by progressive retinal ganglion cell (RGC) axons degeneration and death. The pathogenesis of primary open-angle glaucoma (OAG), the most common type, is still largely unknown and it is often associated with increased intraocular pressure (IOP) although IOP-independent mechanisms play also a role. Neurodegenerative process, including oxidative stress, excitotoxicity and neuroinflammation, and an impaired ocular blood flow are examples of mechanisms supposed to contribute to the IOP independent deterioration in OAG...
November 9, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/29119607/impaired-peripheral-nerve-regeneration-in-type-2-diabetic-mouse-model
#10
Pham Minh Vuong, H Tu Nguyen, Tayo Katano, Shinji Matsumura, Akira Saito, Akihiro Yamada, Hidemasa Furue, Seiji Ito
Peripheral neuropathy is one of the most common and serious complications of type-2 diabetes. Diabetic neuropathy is characterized by a distal symmetrical sensorimotor polyneuropathy, and its incidence increases in patients 40 years of age or older. In spite of extensive research over decades, there are few effective treatments for diabetic neuropathy besides glucose control and improved lifestyle. The earliest changes in diabetic neuropathy occur in sensory nerve fibers, with initial degeneration and regeneration resulting in pain...
November 9, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29118209/in-vivo-imaging-of-cns-injury-and-disease
#11
Katerina Akassoglou, Mario Merlini, Victoria A Rafalski, Raquel Real, Liang Liang, Yunju Jin, Sarah E Dougherty, Vincenzo De Paola, David J Linden, Thomas Misgeld, Binhai Zheng
In vivo optical imaging has emerged as a powerful tool with which to study cellular responses to injury and disease in the mammalian CNS. Important new insights have emerged regarding axonal degeneration and regeneration, glial responses and neuroinflammation, changes in the neurovascular unit, and, more recently, neural transplantations. Accompanying a 2017 SfN Mini-Symposium, here, we discuss selected recent advances in understanding the neuronal, glial, and other cellular responses to CNS injury and disease with in vivo imaging of the rodent brain or spinal cord...
November 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29117435/overview-of-neurotoxicology
#12
Lucio G Costa
The nervous system has a central and primary function in the body, and its relevance and complexity make it a target for a large number of toxic substances. The most common forms of neurotoxicity are the death of neurons (neuronopathy), the degeneration of axons (axonopathy), damage to glial cells (e.g., myelinopathy), and interference with the axonal membrane or neurotransmission. Important neurotoxicants are found among pesticides, metals, solvents, natural substances, and industrial chemicals. Environmental chemicals may also contribute to the etiopathogenesis of neurodevelopmental, neuropsychiatric, and neurodegenerative disorders...
November 8, 2017: Current Protocols in Toxicology
https://www.readbyqxmd.com/read/29117065/reduced-ganglion-cell-volume-on-optical-coherence-tomography-in-patients-with-geographic-atrophy
#13
Hema L Ramkumar, Brian Nguyen, Dirk-Uwe Bartsch, Luke J Saunders, Ilkay Kilic Muftuoglu, Qisheng You, William R Freeman
PURPOSE: Geographic atrophy (GA) is the sequelae of macular degeneration. Automated inner retinal analysis using optical coherence tomography is flawed because segmentation software is calibrated for normal eyes. The purpose of this study is to determine whether ganglion cell layer (GCL) volume is reduced in GA using manual analysis. METHODS: Nineteen eyes with subfoveal GA and 22 controls were selected for morphometric analyses. Heidelberg scanning laser ophthalmoscope optical coherence tomography images of the optic nerve and macula were obtained, and the Viewing Module was used to manually calibrate retinal layer segmentation...
November 7, 2017: Retina
https://www.readbyqxmd.com/read/29114067/regulation-and-dysregulation-of-axon-infrastructure-by-myelinating-glia
#14
REVIEW
Simon Pan, Jonah R Chan
Axon loss and neurodegeneration constitute clinically debilitating sequelae in demyelinating diseases such as multiple sclerosis, but the underlying mechanisms of secondary degeneration are not well understood. Myelinating glia play a fundamental role in promoting the maturation of the axon cytoskeleton, regulating axon trafficking parameters, and imposing architectural rearrangements such as the nodes of Ranvier and their associated molecular domains. In the setting of demyelination, these changes may be reversed or persist as maladaptive features, leading to axon degeneration...
November 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29110997/spinal-nerve-involvement-in-early-guillain-barr%C3%A3-syndrome-the-haymaker-and-kernohan-s-legacy
#15
REVIEW
José Berciano
Pathological studies of early Guillain-Barré syndrome (GBS), defined as of 10days of disease onset, are scanty making it difficult to interpret the physiopathology of clinical and electrophysiological features. In 1949, Webb Haymaker and James Kernohan reported 50 clinico-pathological studies of fatal GBS cases, 32 of them having died between days 2 and 10 after onset. They established that the brunt of initial lesions, consisting of endoneurial oedema interpreted as degenerative, relied on spinal nerves. That this oedema was inflammatory was soon thereafter recognized...
November 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29109681/tenascins-in-retinal-and-optic-nerve-neurodegeneration
#16
REVIEW
Jacqueline Reinhard, Lars Roll, Andreas Faissner
Tenascins represent key constituents of the extracellular matrix (ECM) with major impact on central nervous system (CNS) development. In this regard, several studies indicate that they play a crucial role in axonal growth and guidance, synaptogenesis and boundary formation. These functions are not only important during development, but also for regeneration under several pathological conditions. Additionally, tenascin-C (Tnc) represents a key modulator of the immune system and inflammatory processes. In the present review article, we focus on the function of Tnc and tenascin-R (Tnr) in the diseased CNS, specifically after retinal and optic nerve damage and degeneration...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29109263/phosphatidylserine-save-me-signals-drive-functional-recovery-of-severed-axons-in-caenorhabditis-elegans
#17
Zehra C Abay, Michelle Yu-Ying Wong, Jean-Sébastien Teoh, Tarika Vijayaraghavan, Massimo A Hilliard, Brent Neumann
Functional regeneration after axonal injury requires transected axons to regrow and reestablish connection with their original target tissue. The spontaneous regenerative mechanism known as axonal fusion provides a highly efficient means of achieving targeted reconnection, as a regrowing axon is able to recognize and fuse with its own detached axon segment, thereby rapidly reestablishing the original axonal tract. Here, we use behavioral assays and fluorescent reporters to show that axonal fusion enables full recovery of function after axotomy of Caenorhabditis elegans mechanosensory neurons...
November 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29107592/generation-of-a-motor-nerve-organoid-with-human-stem-cell-derived-neurons
#18
Jiro Kawada, Shohei Kaneda, Takaaki Kirihara, Asif Maroof, Timothée Levi, Kevin Eggan, Teruo Fujii, Yoshiho Ikeuchi
During development, axons spontaneously assemble into a fascicle to form nerves and tracts in the nervous system as they extend within a spatially constrained path. However, understanding of the axonal fascicle has been hampered by lack of an in vitro model system. Here, we report generation of a nerve organoid composed of a robust fascicle of axons extended from a spheroid of human stem cell-derived motor neurons within our custom-designed microdevice. The device is equipped with a narrow channel providing a microenvironment that facilitates the growing axons to spontaneously assemble into a unidirectional fascicle...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29106982/distinct-trka-and-ret-modulated-negative-and-positive-neuropathic-behaviors-in-a-mouse-model-of-resiniferatoxin-induced-small-fiber-neuropathy
#19
Yu-Lin Hsieh, Hung-Wei Kan, Hao Chiang, Yi-Chen Lee, Sung-Tsang Hsieh
Neurotrophic factors and their corresponding receptors play key roles in the maintenance of different phenotypic dorsal root ganglion (DRG) neurons, the axons of which degenerate in small fiber neuropathy, leading to various neuropathic manifestations. Mechanisms underlying positive and negative symptoms of small fiber neuropathy have not been systematically explored. This study investigated the molecular basis of these seemingly paradoxical neuropathic behaviors according to the profiles of TrkA and Ret with immunohistochemical and pharmacological interventions in a mouse model of resiniferatoxin (RTX)-induced small fiber neuropathy...
October 26, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29104820/a-novel-animal-model-for-neuroinflammation-and-white-matter-degeneration
#20
Baohu Ji, Kerin Higa, Virawudh Soontornniyomkij, Atsushi Miyanohara, Xianjin Zhou
Small interference RNA has been widely used to suppress gene expression. Three different short hairpin RNAs (shRNAs) against dopamine D1 receptor (Drd1), driven by mouse U6 promoter in self-complementary AAV8 vector (scAAV8), were used to silence mouse striatal Drd1 expression. Transduction of mouse striatum with all three scAAV8-D1shRNA viruses, but not the control scAAV8 virus, causes extensive neuroinflammation, demyelination, and axon degeneration. RNA interference is known to be coupled to the innate immune system as a host cell defense against virus infection...
2017: PeerJ
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