Iron deposition in Parkinson’s disease by quantitative susceptibility mapping

Chen, Qiqi; Chen, Yi-Ting; Zhang, Yue; Wang, Furu; Yu, Hai Zhou; Zhang, Caiyuan; Jiang, Zhen; Luo, Weifeng

doi:10.1186/s12868-019-0505-9

Cited by 91 publications

(81 citation statements)

References 43 publications

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“…The majority of studies assumed that the SN corresponded to the hypointense region on T2-weighted images between the red nucleus and the cerebral peduncle (8,10,20,23,38). For SWI (12,23,(45)(46)(47)(48)(49)(50)(51)(52) and QSM studies (14,30,31,39,40,(42)(43)(44)(53)(54)(55)(56)(57)(58)(59)(60)(61), all ROIs were manually segmented on the phase or QSM images. Some studies placed ROIs in different subregions of the SN.…”

Section: Regions Of Interest In the Snmentioning

confidence: 99%

“…As for the SWI-based studies, two divided the SN into SNc and SNr (47,51), two in ipsilateral and contralateral SNs (12,49), and one divided the SNc into lateral and medial (23). As for the QSM-based studies, three measured the magnetic susceptibility in the ipsilateral and contralateral SNs (31,53,57), seven in SNc and SNr (30,39,43,54,(56)(57)(58), and two in the anterior and posterior SNs (53,55). The subregion segmentations were mostly performed on QSM images, while one study also used neuromelanin-sensitive imaging to help the SNc delineation (56).…”

Section: Regions Of Interest In the Snmentioning

confidence: 99%

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Iron Imaging as a Diagnostic Tool for Parkinson's Disease: A Systematic Review and Meta-Analysis

et al. 2020

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Background: Parkinson's disease (PD) is a progressive neurodegenerative disease whose main neuropathological feature is the loss of dopaminergic neurons of the substantia nigra (SN). There is also an increase in iron content in the SN in postmortem and imaging studies using iron-sensitive MRI techniques. However, MRI results are variable across studies. Objectives: We performed a systematic meta-analysis of SN iron imaging studies in PD to better understand the role of iron-sensitive MRI quantification to distinguish patients from healthy controls. We also studied the factors that may influence iron quantification and analyzed the correlations between demographic and clinical data and iron load. Methods: We searched PubMed and ScienceDirect databases (from January 1994 to December 2019) for studies that analyzed iron load in the SN of PD patients using T2 * , R2 * , susceptibility weighting imaging (SWI), or quantitative susceptibility mapping (QSM) and compared the values with healthy controls. Details for each study regarding participants, imaging methods, and results were extracted. The effect size and confidence interval (CI) of 95% were calculated for each study as well as the pooled weighted effect size for each marker over studies. Hence, the correlations between technical and clinical metrics with iron load were analyzed. Results: Forty-six articles fulfilled the inclusion criteria including 27 for T2 * /R2 * measures, 10 for SWI, and 17 for QSM (3,135 patients and 1,675 controls). Eight of the articles analyzed both R2 * and QSM. A notable effect size was found in the SN in PD for R2 * increase (effect size: 0.84, 95% CI: 0.60 to 1.08), for SWI measurements (1.14, 95% CI: 0.54 to 1.73), and for QSM increase (1.13, 95% CI: 0.86 to 1.39). Correlations between imaging measures and Unified Parkinson's Disease Rating Scale (UPDRS) scores were mostly observed for QSM. Conclusions: The consistent increase in MRI measures of iron content in PD across the literature using R2 * , SWI, or QSM techniques confirmed that these measurements provided reliable markers of iron content in PD. Several of these measurements correlated with the severity of motor symptoms. Lastly, QSM appeared more robust and reproducible than R2 * and more suited to multicenter studies.

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Section: Regions Of Interest In the Snmentioning

confidence: 99%

Section: Regions Of Interest In the Snmentioning

confidence: 99%

Iron Imaging as a Diagnostic Tool for Parkinson's Disease: A Systematic Review and Meta-Analysis

et al. 2020

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“…Conversely, other studies could not detect an overload of Fe in PD brains [20,21]. Recently, several studies have attempted to determine Fe brain levels in living patients with PD ( [22,23] and references therein). Most but not all studies indicated larger Fe levels in the SN of patients with PD compared to control subjects, whereas no Fe excess was observed in many other brain parts, thus suggesting that a Fe dyshomeostasis occurs in PD brain, especially in the SN [23,24].…”

Section: Parkinson's Disease and Metal Ionsmentioning

confidence: 99%

Metal Chelation Therapy and Parkinson’s Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs

Tosato

Marco

2019

Biomolecules

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The present review reports a list of approximately 800 compounds which have been used, tested or proposed for Parkinson’s disease (PD) therapy in the year range 2014–2019 (April): name(s), chemical structure and references are given. Among these compounds, approximately 250 have possible or established metal-chelating properties towards Cu(II), Cu(I), Fe(III), Fe(II), Mn(II), and Zn(II), which are considered to be involved in metal dyshomeostasis during PD. Speciation information regarding the complexes formed by these ions and the 250 compounds has been collected or, if not experimentally available, has been estimated from similar molecules. Stoichiometries and stability constants of the complexes have been reported; values of the cologarithm of the concentration of free metal ion at equilibrium (pM), and of the dissociation constant Kd (both computed at pH = 7.4 and at total metal and ligand concentrations of 10–6 and 10–5 mol/L, respectively), charge and stoichiometry of the most abundant metal–ligand complexes existing at physiological conditions, have been obtained. A rigorous definition of the reported amounts is given, the possible usefulness of this data is described, and the need to characterize the metal–ligand speciation of PD drugs is underlined.

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“…5 Aberrant iron accumulation in the brain has been reported to be associated with neurodegenerative diseases, such as Alzheimer's diseases (AD), Parkinson's diseases (PD), and Huntington diseases. [6][7][8] Oxidative stress resulting from the accumulated iron triggers neuronal death leading to neurodegeneration; 9 iron being associated with production of reactive oxygen species (ROS), which injure cellular membranes, proteins and deoxyribonucleic acid (DNA). 10 Divalent metal transporter 1 (DMT1/SLC11A2) is an H + -driven multi-metal transporter responsible for transmembrane iron transport; 11 in particular DMT1 has a principle role in transporting iron into the brain.…”

Section: Introductionmentioning

confidence: 99%

Iatrogenic Iron Promotes Neurodegeneration and Activates Self-protection of Neural Cells against Exogenous Iron Attacks

Xia¹,

Liang²,

Li³

et al. 2020

Preprint

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Metal implants are used worldwide, with millions of metal nails, plates and fixtures grafted during orthopaedic surgeries. Iron is the most common element of these metal implants. As time passes metal elements can be corroded and iron can be released from the implants in the form of ferric (Fe 3+ ) or ferrous (Fe 2+ ). These iron ions can permeate the surrounding tissues and enter circulation; importantly both Fe 3+ and Fe 2+ freely pass blood brain barrier (BBB). Can iron from implants represent a risk factor for neurological diseases? This remains an unanswered question. In this study, we discovered that the probability of metal implants delivered through orthopaedic surgeries was higher in patients of Parkinson's diseases (PD) or ischemic stroke than in healthy subjects. This finding instigated subsequent study of iron effects on neuronal cells. In experiments in vivo, we found that iron selectively decreased presence of divalent metal transporter 1 (DMT1) in neurones through increasing the expression of Ndfip1, which degrades DMT1 and rarely exists in glial cells. At the same time iron accumulation increased expression of DMT1 in astrocytes and microglial cells and triggered reactive astrogliosis and microglial activation. Facing the attack of excess iron, glial cells act as neuroprotectors to uptake more extracellular iron by up-regulating DMT1, whereas neurones limit iron uptake through decreasing DMT1 operation. Cerebral accumulation of iron was associated with impaired cognition, locomotion and mood. Excess iron thus affects neural cells and could increase the risk of neurodegeneration.

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Iron deposition in Parkinson’s disease by quantitative susceptibility mapping

Cited by 91 publications

References 43 publications

Iron Imaging as a Diagnostic Tool for Parkinson's Disease: A Systematic Review and Meta-Analysis

Iron Imaging as a Diagnostic Tool for Parkinson's Disease: A Systematic Review and Meta-Analysis

Metal Chelation Therapy and Parkinson’s Disease: A Critical Review on the Thermodynamics of Complex Formation between Relevant Metal Ions and Promising or Established Drugs

Iatrogenic Iron Promotes Neurodegeneration and Activates Self-protection of Neural Cells against Exogenous Iron Attacks

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