Hemosiderin deposition in the brain as footprint of high-altitude cerebral edema

Schommer, Kai; Kallenberg, Kai; Lutz, Kira; Bärtsch, Peter; Knauth, Michael

doi:10.1212/01.wnl.0000435563.84986.78

Cited by 67 publications

(55 citation statements)

References 10 publications

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“…The signal dropout without labeling is likely due to blood products, such as hemosiderin, which are caused by the injection and are known to persist for months after injection. 22,24,25 Persistent signal dropout after needle transplantation of labeled and unlabeled cells is consistent with previous reports and remains a confounding factor for negative-contrast MRI cell tracking. Positive-contrast MRI experiments with iron oxide-labeled cells have been developed and are being investigated to address this problem but are not yet in common use.…”

supporting

confidence: 88%

Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

Umashankar¹,

Corenblum²,

Ray³

et al. 2016

IJN

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An essential component of developing successful neural stem cell (NSC)-based therapies involves the establishment of methodologies to noninvasively monitor grafted NSCs within brain tissues in real time. In this context, ex vivo labeling with ultrasmall superparamagnetic iron oxide (USPIO) particles has been shown to enable efficient tracking of transplanted NSCs via magnetic resonance imaging (MRI). However, whether and how USPIO labeling affects the intrinsic biology of NSCs is not thoroughly understood, and remains an active area of investigation. Here, we perform a comprehensive examination of rat NSC survival and regenerative function upon labeling with the USPIO, Molday ION Rhodamine B (MIRB), which allows for dual magnetic resonance and optical imaging. After optimization of labeling efficiency, two specific doses of MIRB (20 and 50 μg/mL) were chosen and were followed for the rest of the study. We observed that both MIRB doses supported the robust detection of NSCs, over an extended period of time in vitro and in vivo after transplantation into the striata of host rats, using MRI and post hoc fluorescence imaging. Both in culture and after neural transplantation, the higher 50 μg/mL MIRB dose significantly reduced the survival, proliferation, and differentiation rate of the NSCs. Interestingly, although the lower 20 μg/mL MIRB labeling did not produce overtly negative effects, it increased the proliferation and glial differentiation of the NSCs. Additionally, application of this dose also changed the morphological characteristics of neurons and glia produced after NSC differentiation. Importantly, the transplantation of NSCs labeled with either of the two MIRB doses upregulated the immune response in recipient animals. In particular, in animals receiving the 50 μg/mL MIRB-labeled NSCs, this immune response consisted of an increased number of CD68 + -activated microglia, which appeared to have phagocytosed MIRB particles and cells contributing to an exaggerated MRI signal dropout in the animals. Overall, these results indicate that although USPIO particles, such as MIRB, may have advantageous labeling and magnetic resonance-sensitive features for NSC tracking, a further examination of their effects might be necessary before they can be used in clinical scenarios of cell-based transplantation.

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supporting

confidence: 88%

Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

Umashankar¹,

Corenblum²,

Ray³

et al. 2016

IJN

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“…Brain MRI performed at low altitude immediately after rescue by helicopter showed oedema in the corpus callosum [19]. Susceptibility-weighted MRI demonstrated a leak of the blood-brain barrier for erythrocytes as evidenced by hemosiderin deposition persisting over years in the corpus callosum and throughout the brain in more severe cases after HACE (figure 1) [20].…”

Section: Ams and Hacementioning

confidence: 99%

Acute high-altitude sickness

2017

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At any point 1-5 days following ascent to altitudes ⩾2500 m, individuals are at risk of developing one of three forms of acute altitude illness: acute mountain sickness, a syndrome of nonspecific symptoms including headache, lassitude, dizziness and nausea; high-altitude cerebral oedema, a potentially fatal illness characterised by ataxia, decreased consciousness and characteristic changes on magnetic resonance imaging; and high-altitude pulmonary oedema, a noncardiogenic form of pulmonary oedema resulting from excessive hypoxic pulmonary vasoconstriction which can be fatal if not recognised and treated promptly. This review provides detailed information about each of these important clinical entities. After reviewing the clinical features, epidemiology and current understanding of the pathophysiology of each disorder, we describe the current pharmacological and nonpharmacological approaches to the prevention and treatment of these diseases.

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“…Though, it is unclear whether these iron deposits are inflicting the normal brain physiology, which needs to be further investigated. Recent human studies have suggested such deposits to be a footprint of HA cerebral edema pathology (Kallenberg et al, 2008;Schommer et al, 2013).…”

Section: Hh-induced Structural Changes In Hippocampusmentioning

confidence: 99%

Investigation of prolonged hypobaric hypoxia-induced change in rat brain using T2 relaxometry and diffusion tensor imaging at 7T

et al. 2015

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Hemosiderin deposition in the brain as footprint of high-altitude cerebral edema

Abstract: MHs detectable by susceptibility-weighted MRI predominantly in the splenium of the CC are long-lasting footprints of HACE.

Cited by 67 publications

References 10 publications

Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

Acute high-altitude sickness

Investigation of prolonged hypobaric hypoxia-induced change in rat brain using T2 relaxometry and diffusion tensor imaging at 7T

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