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https://www.readbyqxmd.com/read/28539244/manganese-exposure-induces-neuroinflammation-by-impairing-mitochondrial-dynamics-in-astrocytes
#1
Souvarish Sarkar, Emir Malovic, Dilshan S Harischandra, Hilary A Ngwa, Anamitra Ghosh, Colleen Hogan, Dharmin Rokad, Gary Zenitsky, Huajun Jin, Vellareddy Anantharam, Anumantha G Kanthasamy, Arthi Kanthasamy
Chronic manganese (Mn) exposure induces neurotoxicity, which is characterized by Parkinsonian symptoms resulting from impairment in the extrapyramidal motor system of the basal ganglia. Mitochondrial dysfunction and oxidative stress are considered key pathophysiological features of Mn neurotoxicity. Recent evidence suggests astrocytes as a major target of Mn neurotoxicity since Mn accumulates predominantly in astrocytes. However, the primary mechanisms underlying Mn-induced astroglial dysfunction and its role in metal neurotoxicity are not completely understood...
May 21, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28538339/seven-tesla-mri-of-hippocampal-sclerosis-an-in-vivo-feasibility-study-with-histological-correlations
#2
Harald Stefanits, Elisabeth Springer, Ekaterina Pataraia, Christoph Baumgartner, Johannes A Hainfellner, Daniela Prayer, Christian Weisstanner, Thomas Czech, Siegfried Trattnig
INTRODUCTION: Temporal lobe epilepsy (TLE) is the most frequent form of focal epilepsy in adults. Because approximately half of these patients develop drug resistance, epilepsy surgery designed to remove the epileptogenic zone is an excellent option in selected patients. Histopathological analyses of hippocampal specimens in TLE patients revealed 4 types of Ammon's horn sclerosis, which are correlated with long-term epileptological outcome. The aim of this study was the correlation of noninvasive, high-resolution, morphological magnetic resonance imaging (MRI) at an ultra-high-field (7 T) of the hippocampus in TLE patients with histopathological findings...
May 23, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28529876/pathology-of-callosal-damage-in-als-an-ex-vivo-7%C3%A2-t-diffusion-tensor-mri-study
#3
Agustin M Cardenas, Joelle E Sarlls, Justin Y Kwan, Devin Bageac, Zachary S Gala, Laura E Danielian, Abhik Ray-Chaudhury, Hao-Wei Wang, Karla L Miller, Sean Foxley, Saad Jbabdi, Robert C Welsh, Mary Kay Floeter
OBJECTIVES: The goal of this study was to better understand the changes in tissue microstructure that underlie white matter diffusion changes in ALS patients. METHODS: Diffusion tensor imaging was carried out in postmortem brains of 4 ALS patients and two subjects without neurological disease on a 7 T MRI scanner using steady-state free precession sequences. Fractional anisotropy (FA) was measured in the genu, body, and splenium of the corpus callosum in formalin-fixed hemispheres...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28528966/nampt-inhibitor-protects-ischemic-neuronal-injury-in-rat-brain-via-anti-neuroinflammation
#4
Chen-Xiang Chen, Jing Huang, Ga-Qi Tu, Jia-Tong Lu, Xian Xie, Bing Zhao, Ming Wu, Qiao-Juan Shi, San-Hua Fang, Er-Qing Wei, Wei-Ping Zhang, Yun-Bi Lu
Nicotinamide phosphoribosyltransferase (NAMPT) is an important neuroprotective factor in cerebral ischemia, and it has been reported that NAMPT inhibitors can aggravate neuronal injury in the acute phase. However, because it is a cytokine, NAMPT participates in many inflammatory diseases in the peripheral system, and its inhibitors have therapeutic effects. Following cerebral ischemia, the peripheral and resident inflammatory and immune cells produce many pro-inflammatory mediators in the ischemic area, which induce neuroinflammation and impair the brain...
May 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28523763/proton-mr-spectroscopy-of-lesion-evolution-in-multiple-sclerosis-steady-state-metabolism-and-its-relationship-to-conventional-imaging
#5
Ivan I Kirov, Shu Liu, Assaf Tal, William E Wu, Matthew S Davitz, James S Babb, Henry Rusinek, Joseph Herbert, Oded Gonen
Although MRI assessment of white matter lesions is essential for the clinical management of multiple sclerosis, the processes leading to the formation of lesions and underlying their subsequent MRI appearance are incompletely understood. We used proton MR spectroscopy to study the evolution of N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (mI) in pre-lesional tissue, persistent and transient new lesions, as well as in chronic lesions, and related the results to quantitative MRI measures of T1-hypointensity and T2-volume...
May 19, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28512358/delayed-epidural-transplantation-of-human-induced-pluripotent-stem-cell-derived-neural-progenitors-enhances-functional-recovery-after-stroke
#6
I-Hui Lee, Shiang-Suo Huang, Ching-Yu Chuang, Ko-Hsun Liao, Li-Hsin Chang, Chia-Chi Chuang, Yu-Shih Su, Hung-Jui Lin, Jui-Yu Hsieh, Shu-Han Su, Oscar Kuang-Sheng Lee, Hung-Chih Kuo
Induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) are a promising source of tailor-made cell therapy for neurological diseases. However, major obstacles to clinical use still exist. To circumvent complications related to intracerebral administration, we implanted human iPSC-NPCs epidurally over the peri-infarct cortex 7 days after permanent middle cerebral artery occlusion in adult rats. Compared to controls, cell-treated rats showed significant improvements in paretic forelimb usage and grip strength from 10 days post-transplantation (dpt) onwards, as well as reductions in lesion volumes, inflammatory infiltration and astrogliosis at 21 dpt...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28505967/nfatc2-modulates-microglial-activation-in-the-a%C3%AE-pp-ps1-mouse-model-of-alzheimer-s-disease
#7
Gunjan D Manocha, Atreyi Ghatak, Kendra L Puig, Susan D Kraner, Christopher M Norris, Colin K Combs
Alzheimer's disease (AD) brains are characterized by fibrillar amyloid-β (Aβ) peptide containing plaques and associated reactive microglia. The proinflammatory phenotype of the microglia suggests that they may negatively affect disease course and contribute to behavioral decline. This hypothesis predicts that attenuating microglial activation may provide benefit against disease. Prior work from our laboratory and others has characterized a role for the transcription factor, nuclear factor of activated T cells (NFAT), in regulating microglial phenotype in response to different stimuli, including Aβ peptide...
May 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28501505/sevoflurane-postconditioning-attenuates-reactive-astrogliosis-and-glial-scar-formation-after-ischemia-reperfusion-brain-injury
#8
Yong-Ming Zhu, Xue Gao, Yong Ni, Wei Li, Thomas A Kent, Shi-Gang Qiao, Chen Wang, Xiao-Xuan Xu, Hui-Ling Zhang
Cerebral ischemia leads to astrocyte's activation and glial scar formation. Glial scar can inhibit axonal regeneration during the recovery phase. It has demonstrated that sevoflurane has neuroprotective effects against ischemic stroke, but its effects on ischemia-induced formation of astrogliosis and glial scar are unknown. This study was designed to investigate the effect of sevoflurane postconditioning on astrogliosis and glial scar formation in ischemic stroke model both in vivo and in vitro. The results showed that 2...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28500065/loss-of-mpdz-impairs-ependymal-cell-integrity-leading-to-perinatal-onset-hydrocephalus-in-mice
#9
Anja Feldner, M Gordian Adam, Fabian Tetzlaff, Iris Moll, Dorde Komljenovic, Felix Sahm, Tobias Bäuerle, Hiroshi Ishikawa, Horst Schroten, Thomas Korff, Ilse Hofmann, Hartwig Wolburg, Andreas von Deimling, Andreas Fischer
Hydrocephalus is a common congenital anomaly. LCAM1 and MPDZ (MUPP1) are the only known human gene loci associated with non-syndromic hydrocephalus. To investigate functions of the tight junction-associated protein Mpdz, we generated mouse models. Global Mpdz gene deletion or conditional inactivation in Nestin-positive cells led to formation of supratentorial hydrocephalus in the early postnatal period. Blood vessels, epithelial cells of the choroid plexus, and cilia on ependymal cells, which line the ventricular system, remained morphologically intact in Mpdz-deficient brains...
May 12, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28495374/metyrapone-prevents-brain-damage-induced-by-status-epilepticus-in-the-rat-lithium-pilocarpine-model
#10
Luis García-García, Ahmed A Shiha, Rubén Fernández de la Rosa, Mercedes Delgado, Ágata Silván, Pablo Bascuñana, Jens P Bankstahl, Francisca Gomez, Miguel A Pozo
The status epilepticus (SE) induced by lithium-pilocarpine is a well characterized rodent model of the human temporal lobe epilepsy (TLE) which is accompanied by severe brain damage. Stress and glucocorticoids markedly contribute to exacerbate neuronal damage induced by seizures but the underlying mechanisms are poorly understood. Herein we sought to investigate whether a single administration of metyrapone (150 mg/kg, i.p.), an 11β-hydroxylase inhibitor, enzyme involved in the peripheral and central synthesis of corticosteroids, had neuroprotective properties in this model...
May 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28494865/transformation-of-astrocytes-to-a-neuroprotective-phenotype-by-microglia-via-p2y1-receptor-downregulation
#11
Youichi Shinozaki, Keisuke Shibata, Keitaro Yoshida, Eiji Shigetomi, Christian Gachet, Kazuhiro Ikenaka, Kenji F Tanaka, Schuichi Koizumi
Microglia and astrocytes become reactive following traumatic brain injury (TBI). However, the coordination of this reactivity and its relation to pathophysiology are unclear. Here, we show that microglia transform astrocytes into a neuroprotective phenotype via downregulation of the P2Y1 purinergic receptor. TBI initially caused microglial activation in the injury core, followed by reactive astrogliosis in the peri-injured region and formation of a neuroprotective astrocyte scar. Equivalent changes to astrocytes were observed in vitro after injury...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28485037/serotonin-axons-in-the-neocortex-of-the-adult-female-mouse-regrow-after-traumatic-brain-injury
#12
Tymoteusz J Kajstura, Sarah E Dougherty, David J Linden
It is widely held that injured neurons in the central nervous system do not undergo axonal regrowth. However, there is mounting evidence that serotonin axons are a notable exception. Serotonin axons undergo long-distance regrowth in the neocortex after amphetamine lesion, and, following a penetrating stab injury, they can regrow from cut ends to traverse the stab rift. Traumatic brain injury (TBI) is clinically prevalent and can lead to pathologies, such as depression, that are related to serotonergic dysfunction...
May 9, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28476157/microglia-amplify-inflammatory-activation-of-astrocytes-in-manganese-neurotoxicity
#13
Kelly S Kirkley, Katriana A Popichak, Maryam F Afzali, Marie E Legare, Ronald B Tjalkens
BACKGROUND: As the primary immune response cell in the central nervous system, microglia constantly monitor the microenvironment and respond rapidly to stress, infection, and injury, making them important modulators of neuroinflammatory responses. In diseases such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and human immunodeficiency virus-induced dementia, activation of microglia precedes astrogliosis and overt neuronal loss. Although microgliosis is implicated in manganese (Mn) neurotoxicity, the role of microglia and glial crosstalk in Mn-induced neurodegeneration is poorly understood...
May 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28467894/potential-mechanisms-of-development-dependent-adverse-effects-of-the-herbicide-paraquat-in-3d-rat-brain-cell-cultures
#14
J Sandström, A Broyer, D Zoia, C Schilt, C Greggio, M Fournier, K Q Do, F Monnet-Tschudi
Exposure to environmental toxicants during vulnerable windows of brain development is suspected to raise the prevalence for neurological dysfunctions at later stages in life. Differentiation processes and changes in morphology, as well as a lack of physiological barriers, might be reasons that render a developing brain more susceptible to neurotoxicants than an adult. However, also the intrinsic capacity of cells to combat toxicant induced cellular stress might differ between the immature- and mature brain...
April 30, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28466265/ips-cell-cultures-from-a-gerstmann-str%C3%A3-ussler-scheinker-patient-with-the-y218n-prnp-mutation-recapitulate-tau-pathology
#15
Andreu Matamoros-Angles, Lucía Mayela Gayosso, Yvonne Richaud-Patin, Angelique di Domenico, Cristina Vergara, Arnau Hervera, Amaya Sousa, Natalia Fernández-Borges, Antonella Consiglio, Rosalina Gavín, Rakel López de Maturana, Isidro Ferrer, Adolfo López de Munain, Ángel Raya, Joaquín Castilla, Rosario Sánchez-Pernaute, José Antonio Del Río
Gerstmann-Sträussler-Scheinker (GSS) syndrome is a fatal autosomal dominant neurodegenerative prionopathy clinically characterized by ataxia, spastic paraparesis, extrapyramidal signs and dementia. In some GSS familiar cases carrying point mutations in the PRNP gene, patients also showed comorbid tauopathy leading to mixed pathologies. In this study we developed an induced pluripotent stem (iPS) cell model derived from fibroblasts of a GSS patient harboring the Y218N PRNP mutation, as well as an age-matched healthy control...
May 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28462988/synthesis-and-evaluation-of-parenchymal-retention-and-efficacy-of-a-metabolically-stable-o-phosphocholine-n-docosahexaenoyl-l-serine-sirna-conjugate-in-mouse-brain
#16
Mehran Nikan, Maire F Osborn, Andrew H Coles, Annabelle Biscans, Bruno Godinho, Reka Haraszti, Ellen Sapp, Dimas Echeverria, Marian DiFiglia, Neil Aronin, Anastasia Khvorova
Ligand-conjugated siRNAs have potential to achieve targeted delivery and efficient silencing in neurons following local administration in the central nervous system (CNS). We recently described the activity and safety profile of a docosahexaenoic acid (DHA)-conjugated, hydrophobic siRNA (DHA-hsiRNA) targeting Huntingtin (Htt) mRNA in mouse brain. Here, we report the synthesis of an amide-modified, phosphocholine-containing DHA-hsiRNA conjugate (PC-DHA-hsiRNA), which closely resembles the endogenously esterified biological structure of DHA...
May 2, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28461173/poly-adp-ribose-polymerase-1-regulates-microglia-mediated-decrease-of-endothelial-tight-junction-integrity
#17
Abbas Rezaeian Mehrabadi, Minna A Korolainen, Gary Odero G, Donald W Miller, Tiina M Kauppinen
Alzheimer's disease pathology includes, beside neuronal damage, reactive gliosis and reduced blood-brain barrier (BBB) integrity. Microglia are intimately associated with the BBB and upon AD pathology, pro-inflammatory responses of microglia could contribute to BBB damage. To study whether microglia can directly affect BBB integrity, the effects of amyloid beta (Aβ) -stimulated primary murine microglia on co-cultured mouse brain endothelial cells (bEnd3) and murine astrocyte cultures were assessed. We also assessed whether microglial phenotype modulation via poly(ADP-ribose) polymerase-1 (PARP-1) inhibition/ablation can reverse microglial impact on these BBB forming cells...
April 28, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28459434/mice-deficient-in-nrros-show-abnormal-microglial-development-and-neurological-disorders
#18
Kit Wong, Rajkumar Noubade, Paolo Manzanillo, Naruhisa Ota, Oded Foreman, Jason A Hackney, Brad A Friedman, Rajita Pappu, Kimberly Scearce-Levie, Wenjun Ouyang
Microglia and other tissue-resident macrophages within the central nervous system (CNS) have essential roles in neural development, inflammation and homeostasis. However, the molecular pathways underlying their development and function remain poorly understood. Here we report that mice deficient in NRROS, a myeloid-expressed transmembrane protein in the endoplasmic reticulum, develop spontaneous neurological disorders. NRROS-deficient (Nrros(-/-)) mice show defects in motor functions and die before 6 months of age...
May 1, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28456941/activation-of-glucagon-like-peptide-1-receptor-promotes-neuroprotection-in-experimental-autoimmune-encephalomyelitis-by-reducing-neuroinflammatory-responses
#19
Chi-Ho Lee, Se Jin Jeon, Kyu Suk Cho, Eunjung Moon, Arjun Sapkota, Hee Sook Jun, Jong Hoon Ryu, Ji Woong Choi
The signaling axis of glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) has been an important component in overcoming diabetes, and recent reports have uncovered novel beneficial roles of this signaling axis in central nervous system (CNS) disorders, such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia, accelerating processes for exendin-4 repositioning. Here, we studied whether multiple sclerosis (MS) could be a complement to the CNS disorders that are associated with the GLP-1/GLP-1R signaling axis...
April 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28456012/neuregulin-1-positively-modulates-glial-response-and-improves-neurological-recovery-following-traumatic-spinal-cord-injury
#20
Arsalan Alizadeh, Scott M Dyck, Hardeep Kataria, Ghazaleh M Shahriary, Dung H Nguyen, Kallivalappil T Santhosh, Soheila Karimi-Abdolrezaee
Spinal cord injury (SCI) results in glial activation and neuroinflammation, which play pivotal roles in the secondary injury mechanisms with both pro- and antiregeneration effects. Presently, little is known about the endogenous molecular mechanisms that regulate glial functions in the injured spinal cord. We previously reported that the expression of neuregulin-1 (Nrg-1) is acutely and chronically declined following traumatic SCI. Here, we investigated the potential ramifications of Nrg-1 dysregulation on glial and immune cell reactivity following SCI...
April 29, 2017: Glia
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