Abstract:
BACKGROUND:The cystine/glutamate antiporter (xc-) has been implicated in several neurological disorders and, specifically, in multiple sclerosis (MS) as a mediator of glutamate excitotoxicity and proinflammatory immune responses. We aimed to evaluate an xc-specific positron emission tomography (PET) radiotracer, (4S)-4-(3-[18F]fluoropropyl)-L-glutamate ([18F]FSPG), for its ability to allow non-invasive monitoring of xc- activity in a mouse model of MS. METHODS:Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG35-55) peptide in complete Freund's adjuvant (CFA) followed by pertussis toxin. Control mice received CFA emulsion and pertussis toxin without MOG peptide, while a separate cohort of naïve mice received no treatment. PET studies were performed to investigate the kinetics and distribution of [18F]FSPG in naïve, control, pre-symptomatic, and symptomatic EAE mice, compared to 18F-fluorodeoxyglucose ([18F]FDG). After final PET scans, each mouse was perfused and radioactivity in dissected tissues was measured using a gamma counter. Central nervous system (CNS) tissues were further analyzed using ex vivo autoradiography or western blot. [18F]FSPG uptake in human monocytes, and T cells pre- and post-activation was investigated in vitro. RESULTS:[18F]FSPG was found to be more sensitive than [18F]FDG at detecting pathological changes in the spinal cord and brain of EAE mice. Even before clinical signs of disease, a small but significant increase in [18F]FSPG signal was observed in the spinal cord of EAE mice compared to controls. This increase in PET signal became more pronounced in symptomatic EAE mice and was confirmed by ex vivo biodistribution and autoradiography. Likewise, in the brain of symptomatic EAE mice, [18F]FSPG uptake was significantly higher than controls, with the largest changes observed in the cerebellum. Western blot analyses of CNS tissues revealed a significant correlation between light chain of xc- (xCT) protein levels, the subunit of xc- credited with its transporter activity, and [18F]FSPG-PET signal. In vitro [18F]FSPG uptake studies suggest that both activated monocytes and T cells contribute to the observed in vivo PET signal. CONCLUSION:These data highlight the promise of [18F]FSPG-PET as a technique to provide insights into neuroimmune interactions in MS and the in vivo role of xc- in the development and progression of this disease, thus warranting further investigation.
journal_name
J Neuroinflammationjournal_title
Journal of neuroinflammationauthors
Hoehne A,James ML,Alam IS,Ronald JA,Schneider B,D'Souza A,Witney TH,Andrews LE,Cropper HC,Behera D,Gowrishankar G,Ding Z,Wyss-Coray T,Chin FT,Biswal S,Gambhir SSdoi
10.1186/s12974-018-1080-1subject
Has Abstractpub_date
2018-02-22 00:00:00pages
55issue
1issn
1742-2094pii
10.1186/s12974-018-1080-1journal_volume
15pub_type
杂志文章abstract:BACKGROUND:Acute spinal cord injury (SCI) could cause mainly two types of pathological sequelae, the primary mechanical injury, and the secondary injury. The macrophage in SCI are skewed toward the M1 phenotype that might cause the failure to post-SCI repair. METHODS:SCI model was established in Balb/c mice, and the c...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-01805-5
更新日期:2020-04-28 00:00:00
abstract:BACKGROUND:Oxidative stress plays an important and causal role in the mechanisms by which ischemia/reperfusion (I/R) injury increases brain damage after stroke. Accordingly, reducing oxidative stress has been proposed as a therapeutic strategy for limiting damage in the brain after stroke. Myeloperoxidase (MPO) is a hi...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0583-x
更新日期:2016-05-24 00:00:00
abstract:BACKGROUND:HIV-infected individuals are at an increased risk of developing neurological abnormalities. HIV induces neurotoxicity by host cellular factors and individual viral proteins. Some of these proteins including viral protein R (Vpr) promote immune activation and neuronal damage. Vpr is known to contribute to cel...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-11-53
更新日期:2014-03-22 00:00:00
abstract:BACKGROUND:Obesity can lead to cognitive dysfunction including poor performance in memory tasks. However, poor memory is not seen in all obese humans and takes several months to develop in animal models, indicating the adult brain is relatively resistant to obesity's cognitive effects. We have seen that, in the rat, ov...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0578-7
更新日期:2016-05-18 00:00:00
abstract:BACKGROUND:Traumatic brain injury (TBI) is a common pathological condition that presently lacks a specific pharmacological treatment. Adenosine levels rise following TBI, which is thought to be neuroprotective against secondary brain injury. Evidence from stroke and inflammatory disease models suggests that adenosine s...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-020-02009-7
更新日期:2020-11-12 00:00:00
abstract:BACKGROUND:Rasmussen encephalitis (RE) is a rare neuroinflammatory disease characterized by intractable seizures and progressive atrophy on one side of the cerebrum. Perivascular cuffing and clusters of T cells in the affected cortical hemisphere are indicative of an active cellular immune response. METHODS:Peripheral...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0352-2
更新日期:2015-07-19 00:00:00
abstract::The excitotoxin quinolinic acid, a by-product of the kynurenine pathway, is known to be involved in several neurological diseases including multiple sclerosis (MS). Quinolinic acid levels are elevated in experimental autoimmune encephalomyelitis rodents, the widely used animal model of MS. Our group has also found pat...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-014-0204-5
更新日期:2014-12-13 00:00:00
abstract:BACKGROUND:Mer tyrosine kinase (MerTK) activity necessary for amyloid-stimulated phagocytosis strongly implicates that MerTK dysregulation might contribute to chronic inflammation implicated in Alzheimer's disease (AD) pathology. However, the precise mechanism involved in the regulation of MerTK expression by amyloid-β...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1112-x
更新日期:2018-03-12 00:00:00
abstract:BACKGROUND:FTY720 (fingolimod, Gilenya) is a daily oral therapy for multiple sclerosis that readily accesses the central nervous system (CNS). FTY720 is a structural analog to the sphingolipid sphingosine-1-phosphate (S1P) and is a cognate ligand for the S1P G-protein coupled receptors (S1PR). Studies in experimental a...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-10-41
更新日期:2013-03-19 00:00:00
abstract:BACKGROUND:Neurogenic inflammation is orchestrated by a large number of neuropeptides. Tachykinins (substance P, neurokinin A and neurokinin B) are pro-inflammatory neuropeptides that may play an important role in some autoimmune neuroinflammatory diseases. Autoimmunity may have a role in the pathogenesis of autism in ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-180
更新日期:2011-12-21 00:00:00
abstract:BACKGROUND:Leukocytes are believed to be involved in delayed cell death following traumatic brain injury (TBI). However, data demonstrating that blood-borne inflammatory cells are present in the injured brain prior to the onset of secondary brain damage have been inconclusive. We therefore investigated both the interac...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-10-32
更新日期:2013-02-28 00:00:00
abstract::BACKGROUND: Roles for excitotoxicity and inflammation in Alzheimer's disease have been hypothesized. Proinflammatory stimuli, including amyloid beta-peptide (Abeta), elicit a release of glutamate from microglia. We tested the possibility that a coagonist at the NMDA class of glutamate receptors, D-serine, could respon...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-1-2
更新日期:2004-04-20 00:00:00
abstract:BACKGROUND:In schizophrenia, genetic background may provide a substrate for intrinsic maldevelopment of the brain through environmental influences, by recruiting neurotrophic factors and cytokines, to trigger the changes that lead to impaired neuronal functions. Cytokines being the key regulators of immune/inflammatory...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0569-8
更新日期:2016-05-13 00:00:00
abstract:BACKGROUND:Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. OBJECTIVE:We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addr...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-105
更新日期:2011-08-24 00:00:00
abstract:BACKGROUND:Neuroinflammation and a systemic inflammatory reaction are important features of perinatal asphyxia. Neuroinflammation may have dual aspects being a hindrance, but also a significant help in the recovery of the CNS. We aimed to assess intracellular cytokine levels of T-lymphocytes and plasma cytokine levels ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-017-1023-2
更新日期:2017-12-12 00:00:00
abstract:BACKGROUND:Data indicates anti-oxidant, anti-inflammatory and pro-cognitive properties of noradrenaline and analyses of post-mortem brain of Alzheimer's disease (AD) patients reveal major neuronal loss in the noradrenergic locus coeruleus (LC), the main source of CNS noradrenaline (NA). The LC has projections to brain ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-4-8
更新日期:2007-02-26 00:00:00
abstract:BACKGROUND:Activation of NADPH oxidase (PHOX) plays a critical role in mediating dopaminergic neuroinflammation. In the present study, we investigated the role of PHOX in methamphetamine (MA)-induced neurotoxic and inflammatory changes in mice. METHODS:We examined changes in mitogen-activated protein kinases (MAPKs), ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0478-x
更新日期:2016-01-18 00:00:00
abstract:BACKGROUND:Discoveries that microglia-mediated neuroinflammation is involved in the pathological process of depression provided a new strategy for novel antidepressant therapy. Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor regulating inflammation and microglial polarization and, therefore, ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0728-y
更新日期:2016-10-04 00:00:00
abstract:BACKGROUND:S100A9 protein (myeloid-related protein MRP14, also referred to as calgranulin B) is a reliable marker of inflammation, an important proinflammatory factor of innate immunity and acts as an additional antimicrobial peptide in the innate immune system. Evidence indicates that S100A9 contributes to Alzheimer's...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-10-68
更新日期:2013-05-30 00:00:00
abstract::An amendment to this paper has been published and can be accessed via the original article. ...
journal_title:Journal of neuroinflammation
pub_type: 已发布勘误
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更新日期:2020-11-24 00:00:00
abstract:BACKGROUND:Complement activation via the lectin activation pathway (LP) has been identified as the key mechanism behind post-ischemic tissue inflammation causing ischemia-reperfusion injury (IRI) which can significantly impact the clinical outcome of ischemic disease. This work defines the contributions of each of the ...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0684-6
更新日期:2016-08-30 00:00:00
abstract:BACKGROUND:Amyloid β (Aβ)-induced vascular dysfunction significantly contributes to the pathogenesis of Alzheimer's disease (AD). Aβ is known to impair endothelial nitric oxide synthase (eNOS) activity, thus inhibiting endothelial nitric oxide production (NO). METHOD:In this study, we investigated Aβ-effects on heat s...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-015-0304-x
更新日期:2015-05-03 00:00:00
abstract::Secretory phospholipase A2-IIA (sPLA2-IIA) is an inflammatory protein known to play a role in the pathogenesis of many inflammatory diseases. Although this enzyme has also been implicated in the pathogenesis of neurodegenerative diseases, there has not been a direct demonstration of its expression in diseased human br...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-3-28
更新日期:2006-10-07 00:00:00
abstract:BACKGROUND:Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with po...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-11-59
更新日期:2014-03-27 00:00:00
abstract:BACKGROUND:Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the pro-inflammatory response in the subarachnoid space. The complement system, wh...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0770-9
更新日期:2017-01-03 00:00:00
abstract:BACKGROUND:Acute traumatic brain injury (TBI) represents one of major causes of mortality and disability in the USA. Neuroinflammation has been regarded both beneficial and detrimental, probably in a time-dependent fashion. METHODS:To address a role for neuroinflammation in brain injury, C57BL/6 mice were subjected to...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0663-y
更新日期:2016-08-25 00:00:00
abstract:BACKGROUND:Neuroinflammation and demyelination have been suggested as mechanisms causing HIV-1 associated neurocognitive disorder (HAND). This cross-sectional cohort study explores the potential role of antibodies to myelin oligodendrocyte glycoprotein (MOG), a putative autoantigen in multiple sclerosis, in the pathoge...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-7-79
更新日期:2010-11-17 00:00:00
abstract:BACKGROUND:Although the acute toxicity of organophosphorus nerve agents is known to result from acetylcholinesterase inhibition, the molecular mechanisms involved in the development of neuropathology following nerve agent-induced seizure are not well understood. To help determine these pathways, we previously used micr...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/1742-2094-8-84
更新日期:2011-07-21 00:00:00
abstract:BACKGROUND:Chorioamnionitis is associated with an increased risk of brain injury in preterm neonates. Inflammatory changes in brain could underlie this injury. Here, we evaluated whether neuroinflammation is induced by chorioamnionitis in a clinically relevant model. METHODS:Rhesus macaque fetuses were exposed to eith...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-016-0706-4
更新日期:2016-09-06 00:00:00
abstract:BACKGROUND:Over the past decades, positron emission tomography (PET) imaging has become an increasingly useful research modality in the field of multiple sclerosis (MS) research, as PET can visualise molecular processes, such as neuroinflammation, in vivo. The second generation PET radioligand [18F]DPA714 binds with hi...
journal_title:Journal of neuroinflammation
pub_type: 杂志文章
doi:10.1186/s12974-018-1352-9
更新日期:2018-11-13 00:00:00