Visualizing manganese in the primate basal ganglia with magnetic resonance imaging

Newland, M. Christopher; Ceckler, Toni L.; Kordower, Jeffrey H.; Weiss, Bernard

doi:10.1016/0014-4886(89)90157-x

Cited by 218 publications

(111 citation statements)

References 21 publications

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“…There is a persistent notion in the literature that manganese accumulates in the brain predominantly in the basal ganglia, while little or no accumulation is typically observed in the neocortex (Dorman et al, 2006;Finkelstein et al, 2008;Kim, 2004;Newland et al, 1989;Normandin et al, 2004). According to a recent study, such differential distribution of manganese in the brain can be explained by preferential manganese transport via cerebrospinal fluid (CSF) and thus a higher manganese uptake in the brain structures adjacent to the ventricles (Bock et al, 2008a).…”

Section: Discussionmentioning

confidence: 99%

Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies

et al. 2010

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Magnetic resonance imaging (MRI) is widely used in basic and clinical research to map the structural and functional organization of the brain. An important need of MR research is for contrast agents that improve soft-tissue contrast, enable visualization of neuronal tracks, and enhance the capacity of MRI to provide functional information at different temporal scales. Unchelated manganese can be such an agent, and manganese-enhanced MRI (MEMRI) can potentially be an excellent technique for localization of brain activity (for review see Silva et al., 2004). Yet, the toxicity of manganese presents a major limitation for employing MEMRI in behavioral paradigms. We have tested systematically the voluntary wheel running behavior of rats after systemic application of MnCl 2 in a dose range of 16-80 mg/kg, which is commonly used in MEMRI studies. The results show a robust dose-dependent decrease in motor performance, which was accompanied by weight loss and decrease in food intake. The adverse effects lasted for up to 7 postinjection days. The lowest dose of MnCl 2 (16 mg/kg) produced minimal adverse effects, but was not sufficient for functional mapping. We have therefore evaluated an alternative method of manganese delivery via osmotic pumps, which provide a continuous and slow release of manganese. In contrast to a single systemic injection, the pump method did not produce any adverse locomotor effects, while achieving a cumulative concentration of manganese (80 mg/kg) sufficient for functional mapping. Thus, MEMRI with such an optimized manganese delivery that avoids toxic effects can be safely applied for longitudinal studies in behaving animals.

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Section: Discussionmentioning

confidence: 99%

Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies

et al. 2010

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“…The first study used monkeys that were administered MnCl 2 by intravenous injection or inhaled aerosol. Regardless of the administration route of MnCl 2 , an increasing signal intensity on MRI is observed in the caudate nucleus, globus pallidus, substantia nigra, ventromedial hypothalamus, and pituitary gland [23]. Even in man, a hyperintense globus pallidus was found in patients receiving long-term total parenteral nutrition therapy that included manganese [24] and in workers exposed to manganese [25][26][27], with these hyperintensities diminishing after cessation of the manganese exposure [25,28,29].…”

Section: Manganesementioning

confidence: 99%

Contribution of metals to brain MR signal intensity: review articles

et al. 2016

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“…Similarly, in monkey studies where adverse effects were detected below 40 mg Mn/Kg, manganese administration was via several high manganese content injections that most likely exceeded homeostatic regulation and produced elevated brain manganese levels (Newland et al 1989). Thus, while cumulative dose may be predictive of toxicity in many cases of elevated exposures, the dosing regimen (nominal dose, frequency and duration of dosing)…”

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confidence: 99%

Adequacy and Consistency of Animal Studies to Evaluate the Neurotoxicity of Chronic Low-Level Manganese Exposure in Humans

Gwiazda

Lucchini

Smith

2007

Journal of Toxicology and Environmental Health, Part A

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The adequacy of existing animal studies to understand the effects of chronic low-level manganese exposures in humans is unclear. Here, a collection of subchronic to chronic rodent and non-human primate studies was evaluated to determine whether there is a consistent dose -response relationship among studies, whether there is a progression of effects with increasing dose, and whether these studies are adequate for evaluating the neurotoxicity of chronic low-level manganese exposures in humans. Neurochemical and behavioral effects were compared along the axis of estimated internal cumulative manganese dose, independent of the route of exposure. In rodents, motor effects emerged at cumulative doses below those where occupationally exposed humans start to show motor deficits. The main neurochemical effects in rodents were an increase in striatal GABA concentration throughout the internal cumulative dose range of 18 to 5300 mg Mn/Kg but a variable effect on striatal dopamine concentration emerging at internal cumulative doses above ~200 mg Mn/Kg. Monkey studies showed motor deficits and effects on the globus pallidus at relatively low doses and consistent harmful effects on both the globus pallidus and the caudate and putamen at higher doses (> 260 mg Mn/Kg). Internal cumulative manganese doses of animal studies extend more than two orders of magnitude (<1 to 5300 mg Mn/Kg) above the doses at which occupationally exposed humans show neurological dysfunction (10-15 mg Mn/Kg). Since the animal data indicate that manganese neurotoxicity may be different at low compared to elevated exposures, most existing animal model studies might be of 3 limited relevance for the risk assessment of chronic low-level manganese exposure to humans. 4

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Visualizing manganese in the primate basal ganglia with magnetic resonance imaging

Cited by 218 publications

References 21 publications

Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies

Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies

Contribution of metals to brain MR signal intensity: review articles

Adequacy and Consistency of Animal Studies to Evaluate the Neurotoxicity of Chronic Low-Level Manganese Exposure in Humans

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