Intracerebral injection of AMPA causes axonal damage in vivo

2003 ◽  
Vol 991 (1-2) ◽  
pp. 104-112 ◽  
Author(s):  
Jill H. Fowler ◽  
Eileen McCracken ◽  
Deborah Dewar ◽  
James McCulloch
Brain ◽  
1995 ◽  
Vol 118 (3) ◽  
pp. 753-758 ◽  
Author(s):  
Fernando Cendes ◽  
Frederick Andermann ◽  
Kenneth Silver ◽  
Douglas L. Arnold

2021 ◽  
Author(s):  
The Michael J Fox Foundation Pff Standardization Consortium

This is a consensus protocol developed through discussions with Laura Volpicelli-Daley, Caryl Sortwell, Kelvin Luk, Lindsey Gottler, and Virginia Lee. This protocol is intended for research purposes only, using specially-formulated monomeric alpha-synuclein protein available for purchase at Proteos, Inc as the result of efforts by The Michael J. Fox Foundation (MJFF). Each batch of the “Alpha-Synuclein Monomer Protein for Making Pre- Formed Fibrils” has undergone internal purification and quality control at Proteos in addition to external validation to confirm successful generation of pathogenic aSyn PFFs. See Reference section for methods and results from application of alpha-synuclein pre-formed fibrils (aSyn PFFs) in primary neuron cultures in vitro or in mice in vivo. This protocol is referenced in the Polinski et al 2018 paper entitled "Best Practices for Generating and Using Alpha-Synuclein Pre-Formed Fibrils to Model Parkinson's Disease in Rodents" (doi: 10.3233/JPD-171248).


2006 ◽  
Vol 200 (2) ◽  
pp. 509-520 ◽  
Author(s):  
Daniel J. Cuthill ◽  
Jill H. Fowler ◽  
James McCulloch ◽  
Deborah Dewar

2019 ◽  
Vol 116 (20) ◽  
pp. 10130-10139 ◽  
Author(s):  
Rhonda R. Voskuhl ◽  
Noriko Itoh ◽  
Alessia Tassoni ◽  
Macy Akiyo Matsukawa ◽  
Emily Ren ◽  
...  

Regional differences in neurons, astrocytes, oligodendrocytes, and microglia exist in the brain during health, and regional differences in the transcriptome may occur for each cell type during neurodegeneration. Multiple sclerosis (MS) is multifocal, and regional differences in the astrocyte transcriptome occur in experimental autoimmune encephalomyelitis (EAE), an MS model. MS and EAE are characterized by inflammation, demyelination, and axonal damage, with minimal remyelination. Here, RNA-sequencing analysis of MS tissues from six brain regions suggested a focus on oligodendrocyte lineage cells (OLCs) in corpus callosum. Olig1-RiboTag mice were used to determine the translatome of OLCs in vivo in corpus callosum during the remyelination phase of a chronic cuprizone model with axonal damage. Cholesterol-synthesis gene pathways dominated as the top up-regulated pathways in OLCs during remyelination. In EAE, remyelination was induced with estrogen receptor-β (ERβ) ligand treatment, and up-regulation of cholesterol-synthesis gene expression was again observed in OLCs. ERβ-ligand treatment in the cuprizone model further increased cholesterol synthesis gene expression and enhanced remyelination. Conditional KOs of ERβ in OLCs demonstrated that increased cholesterol-synthesis gene expression in OLCs was mediated by direct effects in both models. To address this direct effect, ChIP assays showed binding of ERβ to the putative estrogen-response element of a key cholesterol-synthesis gene (Fdps). As fetal OLCs are exposed in utero to high levels of estrogens in maternal blood, we discuss how remyelinating properties of estrogen treatment in adults during injury may recapitulate normal developmental myelination through targeting cholesterol homeostasis in OLCs.


2012 ◽  
Vol 18 (8) ◽  
pp. 1058-1067 ◽  
Author(s):  
J van Horssen ◽  
ME Witte ◽  
O Ciccarelli

Axonal injury is a key feature of multiple sclerosis (MS) pathology and is currently seen as the main correlate for permanent clinical disability. Although little is known about the pathogenetic mechanisms that drive axonal damage and loss, there is accumulating evidence highlighting the central role of mitochondrial dysfunction in axonal degeneration and associated neurodegeneration. The aim of this topical review is to provide a concise overview on the involvement of mitochondrial dysfunction in axonal damage and destruction in MS. Hereto, we will discuss putative pathological mechanisms leading to mitochondrial dysfunction and recent imaging studies performed in vivo in patients with MS. Moreover, we will focus on molecular mechanisms and novel imaging studies that address the role of mitochondrial metabolism in tissue repair. Finally, we will briefly review therapeutic strategies aimed at improving mitochondrial metabolism and function under neuroinflammatory conditions.


1982 ◽  
Vol 249 (1) ◽  
pp. 167-172 ◽  
Author(s):  
Michael P. Brazell ◽  
Charles A. Marsden

2007 ◽  
Vol 293 (5) ◽  
pp. C1698-C1708 ◽  
Author(s):  
Y. Jeffrey Wu ◽  
Leslie L. Muldoon ◽  
Csanad Varallyay ◽  
Sheila Markwardt ◽  
Richard E. Jones ◽  
...  

Cellular labeling with ferumoxides (Feridex IV) superparamagnetic iron oxide nanoparticles can be used to monitor cells in vivo by MRI. The objective of this study was to use histology and MRI to evaluate an in vivo, as opposed to in vitro, technique for labeling of mononuclear leukocytes as a means of tracking inflammatory processes in the brain. Long-Evans rats were intravenously injected with 20 mg/kg ferumoxides, ferumoxtran-10, or ferumoxytol with or without protamine sulfate. Leukocytes and splenocytes were evaluated by cell sorting and iron histochemistry or were implanted into the brain for MRI. Injection of ferumoxides/protamine sulfate complex IV resulted in iron labeling of leukocytes (ranging from 7.4 ± 0.5% to 12.5 ± 0.9% with average 9.2 ± 0.8%) compared with ferumoxides (ranging from 3.9 ± 0.4% to 6.3 ± 0.5% with average 5.0 ± 0.5%) or protamine sulfate alone (ranging from 0% to 0.9 ± 0.7% with average 0.3 ± 0.3%). Cell sorting analysis indicated that iron-labeled cells were enriched for cell types positive for the myelomonocytic marker (CD11b/c) and the B lymphocyte marker (CD45RA) and depleted in the T cell marker (CD3). Neither ferumoxtran-10 nor ferumoxytol with protamine sulfate labeled leukocytes. In vivo ferumoxides/protamine sulfate-loaded leukocytes and splenocytes were detected by MRI after intracerebral injection. Ferumoxides/protamine complex labeled CD45RA-positive and CD11b/c-positive leukocytes in vivo without immediate toxicity. The dose of feumoxides in this report is much higher than the approved human dose, so additional animal studies are required before this approach could be translated to the clinic. These results might provide useful information for monitoring leukocyte trafficking into the brain.


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