Continuous infusion of manganese improves contrast and reduces side effects in manganese-enhanced magnetic resonance imaging studies

Poole, Dana S.; Doorenweerd, N.; Plomp, Jaap J.; Mahfouz, Ahmed; Reinders, Marcel J. T.; Weerd, Louise van der

doi:10.1016/j.neuroimage.2016.09.030

Cited by 20 publications

(36 citation statements)

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“…Recent studies have investigated an alternative approach for systemic MnCl 2 delivery. In rodents, continuous infusion of MnCl 2 via subcutaneously implanted mini-osmotic pumps has been shown to produce similarly enhanced tissue contrast in T1-weighted images with minimal behavioural abnormalities [32,33,12,34]. For instance, continuous infusion of 60 mg/kg/day MnCl 2 produced high contrast after 5-8 days, with no impact on muscle strength or cortisone levels [34].…”

Section: Introductionmentioning

confidence: 99%

“…In rodents, continuous infusion of MnCl 2 via subcutaneously implanted mini-osmotic pumps has been shown to produce similarly enhanced tissue contrast in T1-weighted images with minimal behavioural abnormalities [32,33,12,34]. For instance, continuous infusion of 60 mg/kg/day MnCl 2 produced high contrast after 5-8 days, with no impact on muscle strength or cortisone levels [34]. Likewise, delivering a cumulative dose of 80 mg/kg MnCl 2 over 7 days produced sufficient contrast and avoided the impact on voluntary wheel running observed with IP delivery [12].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies using osmotic pumps to deliver MnCl 2 have typically delivered a high daily dose over a short period of time or a very low daily dose over a prolonged period [32]. Additionally, with the exception of Sepulveda et al, [33], the few Abbreviations: MEMRI: manganese enhanced magnetic resonance imaging, IP: intraperitoneal, MnCl 2 : manganese chloride, Mn 2+ :manganese, SNR: signal-to-noise ratio, ROI: region of interest, HC: hippocampus, OB: olfactory bulbs, CB: cerebellar cortex, TH: thalamus studies examining the use of osmotic pumps have imaged animals only at 2-3 timepoints [34,32]. A protocol that results in sufficient signal enhancement both immediately (2-4 days) after osmotic pump implantation and over longer time periods (1-3 weeks) has not yet been described, to our knowledge.…”

Section: Introductionmentioning

confidence: 99%

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Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

et al. 2018

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Manganese-enhanced magnetic resonance imaging (MEMRI) is a widely used technique in rodent neuroimaging studies. Traditionally, Mn is delivered to animals via a systemic injection; however, this can lead to toxic effects at high doses. Recent studies have shown that subcutaneously implanted mini-osmotic pumps can be used to continuously deliver manganese chloride (MnCl), and that they produce satisfactory contrast while circumventing many of the toxic side effects. However, neither the time-course of signal enhancement nor the effect of continuous Mn delivery on behaviour, particularly learning and memory, have been well-characterized. Here, we investigated the effect of MnCl dose and route of administration on a) spatial learning in the Morris Water Maze and b) tissue signal enhancement in the mouse brain. Even as early as 3 days after pump implantation, infusion of 25-50 mg/kg/day MnCl via osmotic pump produced signal enhancement as good as or better than that achieved 24 h after a single 50 mg/kg intraperitoneal injection. Neither route of delivery nor MnCl dose adversely affected spatial learning and memory on the water maze. However, especially at higher doses, mice receiving MnCl via osmotic pumps developed skin ulceration which limited the imaging window. With these findings, we provide recommendations for route and dose of MnCl to use for different study designs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

et al. 2018

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“…I.p. injections of 70 mg/kg manganese has previously been shown to significantly increase manganese levels in the basal ganglia (Dodd et al, 2005), and also is a side-effect of contrast agent for MRI (Poole et al, 2017). Manganese frequently serves as a neuronal contrast agent to enhance functional brain mapping at a higher spatial resolution than typical fMRI studies (Lee et al, 2005).…”

Section: Resultsmentioning

confidence: 99%

Mechanism of manganese dysregulation of dopamine neuronal activity

Lin

Colon-Perez

Sambo

et al. 2019

Preprint

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34 Manganese exposure produces Parkinson's-like neurological symptoms, suggesting a selective 35 dysregulation of dopamine transmission. It is unknown, however, how manganese accumulates in 36 dopaminergic brain regions or how it regulates the activity of dopamine neurons. Our in vivo 37 studies suggest manganese accumulates in dopamine neurons of the ventral tegmental area and 38 substantia nigra via nifedipine-sensitive Ca 2+ channels. Manganese produces a Ca 2+ channel-39 mediated current which increases neurotransmitter release and rhythmic firing activity of 40 dopamine neurons. These increases are prevented by blockade of Ca 2+ channels and depend on 41 downstream recruitment of Ca 2+ -activated potassium channels to the plasma membrane. These 42 findings demonstrate the mechanism of manganese-induced dysfunction of dopamine neurons, and 43 reveal a potential therapeutic target to attenuate manganese-induced impairment of dopamine 44 transmission. 45 46 Significance Statement 47Manganese is a trace element critical to many physiological processes. Overexposure to 48 manganese is an environmental risk factor for neurological disorders such as a Parkinson's disease-49 like syndrome known as manganism. We found manganese dose-dependently increased the 50 excitability of dopamine neurons, decreased the amplitude of action potentials, and narrowed 51 action potential width. Blockade of Ca 2+ channels prevented these effects as well as manganese 52 accumulation in the mouse midbrain in vivo. Our data provide a potential mechanism for 53 manganese-regulation of dopaminergic neurons. 54 55Manganese is a trace element critical to many physiological and developmental processes, 57 including the regulation of macronutrient metabolism, blood glucose, cellular energy, reproduction, 58 digestion, and bone growth (Greene and Madgwick, 1988; Erikson et al., 2005). Manganese is a 59 cofactor for several enzymatic processes and a constituent of metalloenzymes, including arginase, 60 pyruvate carboxylase, and manganese-containing superoxide dismutase (Ashner and Aschner, 61 2005; Ashner et al., 2007; Guilarte, 2010). Except in children on long-term parenteral nutrition or 62 individuals with mutations in the metal transporter SLC39A8 gene, manganese deficiencies are 63 seldom reported (Greene and Madgwick, 1988; Zogzas and Mukhopadhyay, 2017). In contrast, 64 excess manganese accumulation in the brain following environmental exposure is implicated in 65 abnormalities related to the dopaminergic system, including Parkinson-like motor dysfunction 66 (Jankovic, 2005), ataxia (Soriano et al., 2016), and hallucinations (Verhoeven et al., 2011). Animal 67 models of manganism have shown that a single large exposure or prolonged moderate exposure to 68 excess manganese is detrimental to the basal ganglia function (Michalke and Fernsebner 2014; 69 Olanow, 2004), albeit with less understood mechanisms.70 71 Manganese can enter the central nervous system (CNS) through the cerebral spinal fluid or by 72 crossing cerebral capillary...

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“…Some studies have used low-dose, fractional administration methods to achieve good imaging effects while avoiding the toxic side effects of MnCl 2 (26,91,92). Using subcutaneous or intraperitoneal implantation of micro-osmotic pumps to continuously administer low doses of MnCl 2 can produce a better enhancement effect than bolus or fractional administration ( [93][94][95]. Local injections reduce the systemic toxic side effects of manganese but cause certain trauma during the administration process, and the technical requirements for administration are high.…”

Section: Toxicitymentioning

confidence: 99%

Manganese-Enhanced Magnetic Resonance Imaging: Application in Central Nervous System Diseases

Yang

2020

Front. Neurol.

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Manganese-enhanced magnetic resonance imaging (MEMRI) relies on the strong paramagnetism of Mn 2+. Mn 2+ is a calcium ion analog and can enter excitable cells through voltage-gated calcium channels. Mn 2+ can be transported along the axons of neurons via microtubule-based fast axonal transport. Based on these properties, MEMRI is used to describe neuroanatomical structures, monitor neural activity, and evaluate axonal transport rates. The application of MEMRI in preclinical animal models of central nervous system (CNS) diseases can provide more information for the study of disease mechanisms. In this article, we provide a brief review of MEMRI use in CNS diseases ranging from neurodegenerative diseases to brain injury and spinal cord injury.

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Continuous infusion of manganese improves contrast and reduces side effects in manganese-enhanced magnetic resonance imaging studies

Cited by 20 publications

References 36 publications

Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

Continuous manganese delivery via osmotic pumps for manganese-enhanced mouse MRI does not impair spatial learning but leads to skin ulceration

Mechanism of manganese dysregulation of dopamine neuronal activity

Manganese-Enhanced Magnetic Resonance Imaging: Application in Central Nervous System Diseases

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