Proinflammatory cytokines promote glial heme oxygenase‐1 expression and mitochondrial iron deposition: implications for multiple sclerosis

Mehindate, Khalil; Sahlas, Demetrios J.; Frankel, Dov; Mawal, Yogesh; Liberman, Adrienne; Corcos, J.; Dion, S.; Schipper, Hyman M.

doi:10.1046/j.1471-4159.2001.00354.x

Cited by 121 publications

(106 citation statements)

References 51 publications

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“…Under oxidative stress, astrocytes may become rich in iron through an overexpression of heme oxygenase-1, an enzyme that promotes mitochondria iron sequestration. [72][73][74] Thus, the activated iron-rich astrocytes may survive an inflammation and become detectable by MR imaging. 72,75 Furthermore, the manganese-dependent enzymes glutamine synthetase and manganese superoxide dismutase (MnSOD) may be abundant in activated astrocytes.…”

Section: Astrocytesmentioning

confidence: 99%

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

2016

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This article provides an overview of in vivo magnetic resonance (MR) imaging contrasts obtained for mammalian brain in relation to histological knowledge. Emphasis is paid to the (1) significance of high spatial resolution for the optimization of T 1 , T 2 , and magnetization transfer contrast, (2) use of exogenous extra-and intracellular contrast agents for validating endogenous contrast sources, and (3) histological structures and biochemical compounds underlying these contrasts and (4) their relevance to neuroradiology. Comparisons between MR imaging at subnanoliter resolution and histological data indicate that (a) myelin sheaths, (b) nerve cells, and (c) the neuropil are most responsible for observed MR imaging contrasts, while (a) diamagnetic macromolecules, (b) intracellular paramagnetic ions, and (c) extracellular free water, respectively, emerge as the dominant factors. Enhanced relaxation rates due to paramagnetic ions, such as iron and manganese, have been observed for oligodendrocytes, astrocytes, microglia, and blood cells in the brain as well as for nerve cells. Taken together, a plethora of observations suggests that the delineation of specific structures in high-resolution MR imaging of mammalian brain and the absence of corresponding contrasts in MR imaging of the human brain do not necessarily indicate differences between species but may be explained by partial volume effects. Second, paramagnetic ions are required in active cells in vivo which may reduce the magnetization transfer ratio in the brain through accelerated T 1 recovery. Third, reductions of the magnetization transfer ratio may be more sensitive to a particular pathological condition, such as astrocytosis, microglial activation, inflammation, and demyelination, than changes in relaxation. This is because the simultaneous occurrence of increased paramagnetic ions (i.e., shorter relaxation times) and increased free water (i.e., longer relaxation times) may cancel T 1 or T 2 effects, whereas both processes reduce the magnetization transfer ratio.

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Section: Astrocytesmentioning

confidence: 99%

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

2016

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“…Elevated HO-1 expression has been observed in brain tissue from individuals with Alzheimer disease, Parkinson disease, and multiple sclerosis, perhaps reflecting a limited host-protective response against ongoing injury (15)(16)(17). The protective functions of HO-1 have been linked to the enzyme's degradation of heme, a strong prooxidant, and the subsequent generation of the antiinflammatory and antioxidative products, carbon monoxide, biliverdin, and bilirubin (14), although nonenzymatic cytoprotective functions of HO-1 through activation of oxidant-responsive transcription factors have also been proposed (18,19).…”

Section: Introductionmentioning

confidence: 99%

Heme oxygenase-1 deficiency accompanies neuropathogenesis of HIV-associated neurocognitive disorders

Gill¹,

Kovacsics²,

Cross³

et al. 2014

J. Clin. Invest.

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“…In MS, recent research has explored the role of iron in the pathogenesis and neuronal damage by ironinduced oxidative damage. 10 The iron-catalyzed reaction that leads to damage by free radicals has been reported in studies of the pathogenesis of experimental allergic encephalomyelitis (EAE), [11][12][13][14] an animal model of MS, in which an abnormal histopathologic iron staining was often observed in tissues from EAE models.…”

mentioning

confidence: 99%

Quantitative Assessment of Iron Accumulation in the Deep Gray Matter of Multiple Sclerosis by Magnetic Field Correlation Imaging

Jensen²,

Lu³

et al. 2007

American Journal of Neuroradiology

129

118

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Proinflammatory cytokines promote glial heme oxygenase‐1 expression and mitochondrial iron deposition: implications for multiple sclerosis

Abstract: Proin¯ammatory cytokines, pathological iron deposition, and oxidative stress have been implicated in the pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). HO-1 mRNA levels and mitochondrial uptake of [

Cited by 121 publications

References 51 publications

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

Heme oxygenase-1 deficiency accompanies neuropathogenesis of HIV-associated neurocognitive disorders

Quantitative Assessment of Iron Accumulation in the Deep Gray Matter of Multiple Sclerosis by Magnetic Field Correlation Imaging

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