Effects of Intracerebroventricular Injection of Iron Dextran on the Iron Concentration and Divalent Metal Transporter 1 Expression in the Caudate Putamen and Substantia Nigra of Rats

Yu, Peng; Chang, Yan‐Zhong; Miao, Wei; Wang, Shumin; Cui, Rui; Qian, Zhong‐Ming; Ke, Ya; Duan, Xingguang

doi:10.1002/ar.20807

Cited by 6 publications

(4 citation statements)

References 53 publications

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“…24 h after the final administration of nanoliposomes. The animals were perfused through the ascending aorta with ice-cold normal saline (0.9% NaCl) followed by 4% paraformaldehyde in 0.1 M phosphate-buffer (PB, pH 7.2–7.4) [20]. The brain, trachea and lungs were removed, post-fixed with 4% paraformaldehyde for another 1.5–4 h, and then stored overnight in 30% sucrose.…”

Section: Methodsmentioning

confidence: 99%

Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain

et al. 2017

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BackgroundIron deficiency in children can have significant neurological consequences, and iron supplementation is an effective treatment of choice. However, traditional routes of iron supplementation do not allow efficient iron delivery to the brain due to the presence of the blood–brain barrier. So an easily delivered iron formulation with high absorption efficiency potentially could find widespread application in iron deficient infants.ResultsIn this study, we have developed and characterized a nanovesicular formulation of ferric ammonium citrate (ferric ammonium citrate nanoliposomes, FAC-LIP) and have shown that it can increase brain iron levels in rats following nasal administration. FAC was incorporated into liposomes with high efficiency (97%) and the liposomes were small (40 nm) and stable. Following intranasal delivery in rats, FAC-LIP significantly increased the iron content in the olfactory bulb, cerebral cortex, striatum, cerebellum and hippocampus, and was more efficient at doing so than FAC alone. No signs of apoptosis or abnormal cell morphology were observed in the brain following FAC-LIP administration, and there were no significant changes in the levels of SOD and MDA, except in the cerebellum and hippocampus. No obvious morphological changes were observed in lung epithelial cells or tracheal mucosa after nasal delivery, suggesting that the formulation was not overtly toxic.ConclusionsIn this study, nanoscale FAC-LIP proved an effective system delivering iron to the brain, with high encapsulation efficiency and low toxicity in rats. Our studies provide the foundation for more detailed investigations into the applications of niosomal nasal delivery of liposomal formulations of iron as a simple and safe therapy for iron deficiency anemia.Graphical abstractThe diagrammatic sketch of “Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain”. Nanoliposome-encapsulated ferric ammonium citrate (FAC-LIP) was successfully prepared and intranasal administration of FAC-LIP increased both the total iron contents and iron storage protein (FTL) expression in rat olfactory bulb, cerebral cortex, striatum and hippocampus, compared with those of FAC groups. Moreover, there was not overtly toxic affects to brain, lung epithelial cells and tracheal mucosa. Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-017-0277-2) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain

et al. 2017

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“…Non-heme iron was stained with DAB-enhanced iron histochemistry method as previously described [13,14]. After rinsing three times in de-ionized water for 30min, the sections were incubated at room temperature for 20min in 1% H 2 O 2 in 0.01 M phosphate-buffered saline (PBS) to quench endogenous peroxidase activity and then rinsed three times in de-ionized water for 30min.…”

Section: Iron Histochemistrymentioning

confidence: 99%

Effect of Fixative Solutions on Non-Heme Iron Staining in the Brain

Liu¹,

Jin²,

Song

et al. 2018

GJEM

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Objective: Non-heme iron staining is very weak in the brain due to its limited iron contents. In order to optimize the iron staining in the brain, different types of fixation solutions were explored and compared in this study. Methods:The brain tissues were cut from mice and fixed with 95% ethanol, or a mixture of methanol: chloroform: acetic acid (volume ratio is 6:3:1), or Bouin's solution or polyformaldehyde. Then, coronal frozen sections were prepared and iron histochemistry was performed to detect the iron staining in cerebral cortex, hippocampus, cerebellum and choroid plexus. Finally, the images were captured and saved for analysis.Results: It was found that the different types of fixation solutions didn't have obvious influences on iron staining when the incubation time was proper in Perl's staining solution. Conclusion:Optimal iron staining could be achieved with a combination of DAB-enhancement, and fixative solution could be selected according to other considerations in experiments. This provided important data for establishing a steady method for positive iron staining in the brain tissues.

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“…For intracerebroventricular injection (ICV) of Glu, rats were anesthetized with pentobarbital sodium (40 mg/kg, i.p. ), placed in a stereotaxic instrument (SR-6N, Tokyo, Japan) and Glu was injected as previously described, rostral~caudal: 0.8 mm posterior to Bregma, medial ~ lateral: 1.6 mm from the midline, and dorsal~ventral: 3.2 mm from the surface of the dura [23]. Sodium glutamate (Sigma) was administrated into rat lateral ventricle (60 µg and 120 µg, respectively), and the control group received the same volume of artificial cerebrospinal fluid (ACSF).…”

Section: Animals and Treatmentsmentioning

confidence: 99%

“…SN is small in sample size, so its iron contents was detected in cryostat sections with a modified Perl's staining as previously described [23]. SN was cut at thickness of 20 μm and incubated at room temperature for 20 min in 1% H 2 O 2 in 0.01 M phosphate-buffered saline (PBS) to quench endogenous peroxidase activity, then incubated at room temperature for 15 hr in a freshly made Perl's solution [1% potassium ferrocyanide in 1% aqueous hydrochloric acid for ferric iron], and the negative control sections were incubated in Perl's solution with PBS in place of potassium ferrocyanide.…”

Section: Determination Of Non-heme Iron Contents In Brainmentioning

confidence: 99%

Effect of Glutamate on Brain Iron Metabolism and the Regulation Mechanism

Zhang¹,

Di²

2015

J Drug Metab Toxicol

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Glutamate is an excitatory transmitter and can induce neurotoxicity, it can also increase the iron concentrations in the brain, but little is known about the detailed molecular regulation mechanism of iron metabolism by Glu. Based on our previous data, iron metabolism related proteins might be associated with the increase of brain iron contents induced by neurotransmitter. To investigate the issues, the iron contents, non-transferrin-bound iron (NTBI) uptake and the expression of iron uptake and iron release proteins were firstly examined in vivo and in vitro with iron histochemistry, inductively coupled plasma mass spectroscopy (ICP-MS), 55 Fe radioactive liquid scintillation counting and western blot methods. Data showed that glutamate induced the increase of total iron contents, storage iron contents and NTBI uptake activity. Moreover, only divalent metal transporter 1, one of iron uptake proteins, was increased in rat brain and PC12 cells treated with glutamate. Further investigations revealed that nuclear factor кB (NF-кB) and protein kinase C (PKC) were involved in the regulation of DMT1 in PC12 cells treated with glutamate. These findings demonstrate that glutamate increases iron contents in the brain through increased NTBI, and that DMT1 is the key molecule underlying regulation of iron metabolism by glutamate, Furthermore, NF-кB and PKC play important roles in the regulatory pathway of DMT1 expression by glutamate. Thus, it implicates that inhibiting the expression of DMT1 and disruption of its regulation pathway might be effective strategies in attenuating glutamate neurotoxicity through decreased iron contents.

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Effects of Intracerebroventricular Injection of Iron Dextran on the Iron Concentration and Divalent Metal Transporter 1 Expression in the Caudate Putamen and Substantia Nigra of Rats

Cited by 6 publications

References 53 publications

Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain

Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain

Effect of Fixative Solutions on Non-Heme Iron Staining in the Brain

Effect of Glutamate on Brain Iron Metabolism and the Regulation Mechanism

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