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https://www.readbyqxmd.com/read/28434162/isolation-of-astrocytes-displaying-myofibroblast-properties-and-present-in-multiple-sclerosis-lesions
#1
Nicolas Vedrenne, Vincent Sarrazy, Laurence Richard, Nelly Bordeau, Serge Battu, Fabrice Billet, Alexis Desmoulière
A wide heterogeneity of lesions can affect the central nervous system (CNS). In all situations where neurons are damaged, including multiple sclerosis (MS), a common reactive astrocytosis is present. Sedimentation field-flow fractionation (SdFFF) was used to sort astrocyte subpopulations. After SdFFF elution, cells, prepared from rat newborn cortex, were cultured and analyzed by immunocytofluorescence for glial fibrillary acidic protein (GFAP) and α-smooth muscle (SM) actin (a specific marker for myofibroblasts) expression...
April 22, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28420695/adeno-associated-viral-9-mediated-cdk5-inhibitory-peptide-reverses-pathologic-changes-and-behavioral-deficits-in-the-alzheimer-s-disease-mouse-model
#2
Yong He, Suyue Pan, Miaojing Xu, Rongni He, Wei Huang, Pingping Song, Jianou Huang, Han-Ting Zhang, Yafang Hu
Cyclin-dependent kinase 5 (Cdk5), which binds to and is activated by p35, phosphorylates multiple substrates and plays an essential role in the development and function of the CNS; however, proteolytic production of p25 from p35 under stress conditions leads to the inappropriate activation of Cdk5 and contributes to hyperphosphorylation of τ and other substrates that are related to the pathogenesis of Alzheimer's disease. Selective inhibition of aberrant Cdk5 activity via genetic overexpression of Cdk5 inhibitory peptide (CIP) reduces pathologic changes and prevents brain atrophy and memory loss in p25-transgenic mice...
April 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28377875/astrocyte-ikk%C3%AE-nf-%C3%AE%C2%BAb-signaling-is-required-for-diet-induced-obesity-and-hypothalamic-inflammation
#3
J D Douglass, M D Dorfman, R Fasnacht, L D Shaffer, J P Thaler
OBJECTIVE: Obesity and high fat diet (HFD) consumption in rodents is associated with hypothalamic inflammation and reactive gliosis. While neuronal inflammation promotes HFD-induced metabolic dysfunction, the role of astrocyte activation in susceptibility to hypothalamic inflammation and diet-induced obesity (DIO) remains uncertain. METHODS: Metabolic phenotyping, immunohistochemical analyses, and biochemical analyses were performed on HFD-fed mice with a tamoxifen-inducible astrocyte-specific knockout of IKKβ (Gfap(CreER)Ikbkb(fl/fl), IKKβ-AKO), an essential cofactor of NF-κB-mediated inflammation...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28374133/post-natal-deletion-of-neuronal-camp-responsive-element-binding-creb-1-promotes-pro-inflammatory-changes-in-the-mouse-hippocampus
#4
Elisa Marchese, Valentina Di Maria, Daniela Samengo, Giovambattista Pani, Fabrizio Michetti, Maria Concetta Geloso
By taking advantage of a "floxed" conditional CREB mutant mouse (CREB1loxP/loxP), in which postnatal deletion of the Creb gene in the forebrain is driven by the calcium/calmodulin-dependent protein kinase II-α gene (Camk2a) promoter (BCKO mice), we here show that selective disruption of CREB function in adult forebrain neurons results, in adult mice, in morphological alterations at the hippocampal level, including hippocampal shrinkage, reduced somal volume of neurons, microgliosis and mild reactive astrocytosis, mainly involving the CA1 subfield...
April 4, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28372497/astrocyte-mediated-inflammation-in-cortical-spreading-depression
#5
Amir Ghaemi, Leila Alizadeh, Shahnaz Babaei, Maryam Jafarian, Maryam Khaleghi Ghadiri, Sven G Meuth, Stjepana Kovac, Ali Gorji
Background Cortical spreading depression (CSD) related diseases such as migraine, cerebrovascular diseases, and epilepsy have been associated with reactive astrocytosis, yet the mechanisms of these tissue changes remain unclear. CSD-induced inflammatory response has been proposed to play a role in some neurological disorders and thus may also contribute to reactive astrocytosis. Methods Using ex vivo brain slices and in vitro astrocytic cultures, we aimed to characterize CSD related changes in astrocytes and markers of inflammation by immunocyto- and immunohistochemistry...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28372289/dpp4-regulates-the-inflammatory-response-in-a-rat-model-of-febrile-seizures
#6
Qi Sun, Yusong Zhang, Jie Huang, Fang Yu, Jian Xu, Biwen Peng, Wanhong Liu, Song Han, Jun Yin, Xiaohua He
Febrile seizures (FS) are the most common seizure disorders in children aged 6 months to 5 years. Children suffering from complex FS have a high risk of developing subsequent temporal lobe epilepsy (TLE). Neuroinflammation is involved in the pathogenesis of FS although the mechanism remains unknown. Our previous study using the Whole Rat Genome Oligo Microarray determined that Dipeptidyl peptidase IV (DPP4) is potentially a related gene in FS rats. In this study, we demonstrated that DPP4 expression was significantly increased at both the protein and mRNA levels after hyperthermia induction...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28269776/amyloid-related-imaging-abnormalities-in%C3%A2-an-aged-squirrel-monkey-with-cerebral-amyloid-angiopathy
#7
Eric Heuer, Jessica Jacobs, Rebecca Du, Silun Wang, Orion P Keifer, Amarallys F Cintron, Jeromy Dooyema, Yuguang Meng, Xiaodong Zhang, Lary C Walker
Amyloid-related imaging abnormalities (ARIA) in magnetic resonance imaging scans have emerged as indicators of potentially serious side effects in clinical trials of therapeutics for Alzheimer's disease. These anomalies include an edematous type (ARIA-E) that appears as hyperintense (bright) regions by T2-weighted MRI, and a type characterized by the deposition of hemosiderin (ARIA-H) that elicits a hypointense signal, especially in T2* susceptibility weighted images. ARIA in general has been linked to the presence of amyloid-β (Aβ)-type cerebral amyloid angiopathy, an accumulation of misfolded Aβ protein in the vascular wall that impairs the integrity of brain blood vessels...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28255908/nlrp3-inflammasome-inhibitor-ameliorates-amyloid-pathology-in-a-mouse-model-of-alzheimer-s-disease
#8
Jun Yin, Fanpeng Zhao, Jeremy E Chojnacki, Jacob Fulp, William L Klein, Shijun Zhang, Xiongwei Zhu
The activation of the NLRP3 inflammasome signaling pathway plays an important role in the neuroinflammation in Alzheimer's disease (AD). In this study, we investigated the effects of JC-124, a rationally designed NLRP3 inflammasome inhibitor, on AD-related deficits in CRND8 APP transgenic mice (TgCRND8). We first demonstrated increased formation and activation of NLRP3 inflammasome in TgCRND8 mice compared to non-transgenic littermate controls, which was inhibited by the treatment with JC-124. Importantly, JC-124 treatment led to decreased levels of Aβ deposition and decreased levels of soluble and insoluble Aβ1-42 in the brain of CRND8 mice which was accompanied by reduced β-cleavage of APP, reduced activation of microglia but enhanced astrocytosis...
March 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28244955/plasma-soluble-cd163-is-associated-with-postmortem-brain-pathology-in-human-immunodeficiency-virus-infection
#9
Alex K Bryant, David J Moore, Tricia H Burdo, Jessica R Lakritz, Ben Gouaux, Virawudh Soontornniyomkij, Cristian L Achim, Eliezer Masliah, Igor Grant, Andrew J Levine, Ronald J Ellis
OBJECTIVE: Higher plasma soluble cluster of differentiation (CD)163 (sCD163), shed by monocytes and macrophages, correlates with neurocognitive impairment in HIV infection. We hypothesized that higher antemortem plasma or cerebrospinal fluid (CSF) sCD163 would be associated with greater postmortem neurodegeneration and/or microgliosis. DESIGN: Retrospective, postmortem observational study. METHODS: We measured sCD163 levels in antemortem plasma (n = 54) and CSF (n = 32) samples from 74 HIV-seropositive participants (median 5 months before death) who donated their brains to research at autopsy...
April 24, 2017: AIDS
https://www.readbyqxmd.com/read/28237317/a-calpain-inhibitor-ameliorates-seizure-burden-in-an-experimental-model-of-temporal-lobe-epilepsy
#10
Philip M Lam, Jessica Carlsen, Marco I González
In this study, we used the pilocarpine model of epilepsy to evaluate the involvement of calpain dysregulation on epileptogenesis. Detection of spectrin breakdown products (SBDPs, a hallmark of calpain activation) after induction of pilocarpine-induced status epilepticus (SE) and before appearance of spontaneous seizure suggested the existence of sustained calpain activation during epileptogenesis. Acute treatment with a cell permeable inhibitor of calpain, MDL-28170, resulted in a partial but significant reduction on seizure burden...
June 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28223486/serum-borne-bioactivity-caused-by-pulmonary-multiwalled-carbon-nanotubes-induces-neuroinflammation-via-blood-brain-barrier-impairment
#11
Mario J Aragon, Lauren Topper, Christina R Tyler, Bethany Sanchez, Katherine Zychowski, Tamara Young, Guy Herbert, Pamela Hall, Aaron Erdely, Tracy Eye, Lindsey Bishop, Samantha A Saunders, Pretal P Muldoon, Andrew K Ottens, Matthew J Campen
Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) causes indirect systemic inflammation through unknown pathways. MWCNTs translocate only minimally from the lungs into the systemic circulation, suggesting that extrapulmonary toxicity may be caused indirectly by lung-derived factors entering the circulation. To assess a role for MWCNT-induced circulating factors in driving neuroinflammatory outcomes, mice were acutely exposed to MWCNTs (10 or 40 µg/mouse) via oropharyngeal aspiration. At 4 h after MWCNT exposure, broad disruption of the blood-brain barrier (BBB) was observed across the capillary bed with the small molecule fluorescein, concomitant with reactive astrocytosis...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28223366/la-deletion-from-mouse-brain-alters-pre-trna-metabolism-and-accumulation-of-pre-5-8s-rrna-with-neuron-death-and-reactive-astrocytosis
#12
Nathan H Blewett, James R Iben, Sergei Gaidamakov, Richard J Maraia
Human La antigen (Sjögren's syndrome antigen B, SSB) is an abundant multifunctional RNA-binding protein. In the nucleoplasm, La binds to and protects from 3' exonucleases, the ends of precursor-tRNAs and other transcripts synthesized by RNA polymerase III, and facilitates their maturation, while a nucleolar isoform has been implicated in rRNA biogenesis by multiple independent lines of evidence. We showed earlier that conditional La knockout (La cKO) from mouse cortex neurons results in defective tRNA processing although pathway(s) involved in neuronal loss thereafter was unknown...
February 21, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28176234/frequent-mild-head-injury-promotes-trigeminal-sensitivity-concomitant-with-microglial-proliferation-astrocytosis-and-increased-neuropeptide-levels-in-the-trigeminal-pain-system
#13
Ashley L Tyburski, Lan Cheng, Soroush Assari, Kurosh Darvish, Melanie B Elliott
BACKGROUND: Frequent mild head injuries or concussion along with the presence of headache may contribute to the persistence of concussion symptoms. METHODS: In this study, the acute effects of recovery between mild head injuries and the frequency of injuries on a headache behavior, trigeminal allodynia, was assessed using von Frey testing up to one week after injury, while histopathological changes in the trigeminal pain pathway were evaluated using western blot, ELISA and immunohistochemistry...
December 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28133418/effects-of-neural-differentiation-maturity-status-of-human-induced-pluripotent-stem-cells-prior-to-grafting-in-a-subcortical-ischemic-stroke-model
#14
Matthew B Jensen, Lindsey D Jager, Laura K Cohen, Susanna S Kwok, Jin M Kwon, Crystal A Hall, Cassandra Heilingoetter
Neural cell grafting is a promising therapy for stroke, but the optimal differentiation status of the cells prior to grafting is unclear. We grafted cells at different maturity stages (days 28, 42, or 56 of in vitro neural differentiation) into the brains of eight-week-old rats one week after subcortical ischemic stroke, and assessed motor and sensory behavioral recovery over one month. We did not find a difference between the grafted or control groups on behavioral recovery, or on brain tissue outcomes including infarct size, microgliosis, or astrocytosis...
December 2016: Neurology, Psychiatry, and Brain Research
https://www.readbyqxmd.com/read/28124770/the-effect-of-stereotactic-injections-on-demyelination-and-remyelination-a-study-in-the-cuprizone-model
#15
Laura Salinas Tejedor, Tanja Wostradowski, Stefan Gingele, Thomas Skripuletz, Viktoria Gudi, Martin Stangel
Remyelination is the natural repair mechanism in demyelinating disorders of the central nervous system (CNS) such as multiple sclerosis. Several animal models have been used to study demyelination and remyelination. Among toxic animal models, oral administration of the toxin cuprizone leads to white and gray matter demyelination. In contrast, focal demyelination models include the stereotactic application of a toxin such as lysolecithin or ethidium bromide. The injection procedure generates a local disruption of the blood-brain barrier (BBB) and might thus trigger a local inflammatory reaction and consequently may influence demyelination and remyelination...
April 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28121634/fluorodeoxyglucose-positron-emission-tomography-fdg-pet-correlation-of-histopathology-and-mri-in-prion-disease
#16
Karin P Mente, James K O'Donnell, Stephen E Jones, Mark L Cohen, Nicolas R Thompson, Alberto Bizzi, Pierluigi Gambetti, Jiri G Safar, Brian S Appleby
Creutzfeldt-Jakob disease (CJD) and other prion diseases are rapidly progressive spongiform encephalopathies that are invariably fatal. Clinical features and magnetic resonance imaging, electroencephalogram, and cerebrospinal fluid abnormalities may suggest prion disease, but a definitive diagnosis can only be made by means of neuropathologic examination. Fluorodeoxyglucose positron emission tomography (FDG-PET) is not routinely used to evaluate patients with suspected prion disease. This study includes 11 cases of definite prion disease in which FDG-PET scans were obtained...
January 2017: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/28028861/creutzfeldt-jakob-disease
#17
REVIEW
Yasushi Iwasaki
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...
April 2017: 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
#18
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
#19
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...
January 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/27836728/altered-gene-expression-profile-in-a-mouse-model-of-scn8a-encephalopathy
#20
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
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