Visualizing the Potential Impairment of Polymyxin B to Central Nervous System Through MR Susceptibility-Weighted Imaging

Polymyxin B (PMB) exert bactericidal effects on the cell wall of Gram-negative bacteria, leading to changes in the permeability of the cytoplasmic membrane and resulting in cell death, which is sensitive to the multi-resistant Gram-negative bacteria. However, the severe toxicity and adverse side eff...

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Main Authors: Ni Zhang, Lichong Zhu, Qiuhong Ouyang, Saisai Yue, Yichun Huang, Shuang Qu, Runwei Li, Yuanyuan Qiao, Man Xu, Fangfei He, Bin Zhao, Lai Wei, Xiaoai Wu, Peisen Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-12-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.784864/full
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author Ni Zhang
Lichong Zhu
Qiuhong Ouyang
Qiuhong Ouyang
Saisai Yue
Yichun Huang
Shuang Qu
Runwei Li
Yuanyuan Qiao
Man Xu
Fangfei He
Bin Zhao
Lai Wei
Xiaoai Wu
Peisen Zhang
Peisen Zhang
author_facet Ni Zhang
Lichong Zhu
Qiuhong Ouyang
Qiuhong Ouyang
Saisai Yue
Yichun Huang
Shuang Qu
Runwei Li
Yuanyuan Qiao
Man Xu
Fangfei He
Bin Zhao
Lai Wei
Xiaoai Wu
Peisen Zhang
Peisen Zhang
author_sort Ni Zhang
collection DOAJ
description Polymyxin B (PMB) exert bactericidal effects on the cell wall of Gram-negative bacteria, leading to changes in the permeability of the cytoplasmic membrane and resulting in cell death, which is sensitive to the multi-resistant Gram-negative bacteria. However, the severe toxicity and adverse side effects largely hamper the clinical application of PMB. Although the molecular pathology of PMB neurotoxicity has been adequately studied at the cellular and molecular level. However, the impact of PMB on the physiological states of central nervous system in vivo may be quite different from that in vitro, which need to be further studied. Therefore, in the current study, the biocompatible ultra-uniform Fe3O4 nanoparticles were employed for noninvasively in vivo visualizing the potential impairment of PMB to the central nervous system. Systematic studies clearly reveal that the prepared Fe3O4 nanoparticles can serve as an appropriate magnetic resonance contrast agent with high transverse relaxivity and outstanding biosafety, which thus enables the following in vivo susceptibility-weighted imaging (SWI) studies on the PMB-treated mice models. As a result, it is first found that the blood-brain barrier (BBB) of mice may be impaired by successive PMB administration, displaying by the discrete punctate SWI signals distributed asymmetrically across brain regions in brain parenchyma. This result may pave a noninvasive approach for in-depth studies of PMB medication strategy, monitoring the BBB changes during PMB treatment, and even assessing the risk after PMB successive medication in multidrug-resistant Gram-negative bacterial infected patients from the perspective of medical imaging.
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spelling doaj.art-a931a6d3b10d45f095f4fe27b6a6996d2022-12-21T21:19:42ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-12-011210.3389/fphar.2021.784864784864Visualizing the Potential Impairment of Polymyxin B to Central Nervous System Through MR Susceptibility-Weighted ImagingNi Zhang0Lichong Zhu1Qiuhong Ouyang2Qiuhong Ouyang3Saisai Yue4Yichun Huang5Shuang Qu6Runwei Li7Yuanyuan Qiao8Man Xu9Fangfei He10Bin Zhao11Lai Wei12Xiaoai Wu13Peisen Zhang14Peisen Zhang15Department of Psychiatry, and Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, ChinaCollege of Life Science and Technology, Beijing University of Chemical Technology, Beijing, ChinaDepartment of Psychiatry, and Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, ChinaCollege of Life Science and Technology, Beijing University of Chemical Technology, Beijing, ChinaCollege of Life Science and Technology, Beijing University of Chemical Technology, Beijing, ChinaCollege of Life Science and Technology, Beijing University of Chemical Technology, Beijing, ChinaCollege of Life Science and Technology, Beijing University of Chemical Technology, Beijing, ChinaCollege of Life Science and Technology, Beijing University of Chemical Technology, Beijing, ChinaCollege of Life Science and Technology, Beijing University of Chemical Technology, Beijing, ChinaCollege of Life Science and Technology, Beijing University of Chemical Technology, Beijing, ChinaCollege of Life Science and Technology, Beijing University of Chemical Technology, Beijing, ChinaXinxiang Key Laboratory of Forensic Toxicology, School of Forensic Medicine, Xinxiang Medical University, Xinxiang, ChinaXinxiang Key Laboratory of Forensic Toxicology, School of Forensic Medicine, Xinxiang Medical University, Xinxiang, ChinaDepartment of Psychiatry, and Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, ChinaCollege of Life Science and Technology, Beijing University of Chemical Technology, Beijing, ChinaDepartment of Rehabilitation Medicine, School of Medicine, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, ChinaPolymyxin B (PMB) exert bactericidal effects on the cell wall of Gram-negative bacteria, leading to changes in the permeability of the cytoplasmic membrane and resulting in cell death, which is sensitive to the multi-resistant Gram-negative bacteria. However, the severe toxicity and adverse side effects largely hamper the clinical application of PMB. Although the molecular pathology of PMB neurotoxicity has been adequately studied at the cellular and molecular level. However, the impact of PMB on the physiological states of central nervous system in vivo may be quite different from that in vitro, which need to be further studied. Therefore, in the current study, the biocompatible ultra-uniform Fe3O4 nanoparticles were employed for noninvasively in vivo visualizing the potential impairment of PMB to the central nervous system. Systematic studies clearly reveal that the prepared Fe3O4 nanoparticles can serve as an appropriate magnetic resonance contrast agent with high transverse relaxivity and outstanding biosafety, which thus enables the following in vivo susceptibility-weighted imaging (SWI) studies on the PMB-treated mice models. As a result, it is first found that the blood-brain barrier (BBB) of mice may be impaired by successive PMB administration, displaying by the discrete punctate SWI signals distributed asymmetrically across brain regions in brain parenchyma. This result may pave a noninvasive approach for in-depth studies of PMB medication strategy, monitoring the BBB changes during PMB treatment, and even assessing the risk after PMB successive medication in multidrug-resistant Gram-negative bacterial infected patients from the perspective of medical imaging.https://www.frontiersin.org/articles/10.3389/fphar.2021.784864/fullpolymyxin BneurotoxicityFe3O4 nanoparticlesin vivosusceptibility-weighted imaging
spellingShingle Ni Zhang
Lichong Zhu
Qiuhong Ouyang
Qiuhong Ouyang
Saisai Yue
Yichun Huang
Shuang Qu
Runwei Li
Yuanyuan Qiao
Man Xu
Fangfei He
Bin Zhao
Lai Wei
Xiaoai Wu
Peisen Zhang
Peisen Zhang
Visualizing the Potential Impairment of Polymyxin B to Central Nervous System Through MR Susceptibility-Weighted Imaging
Frontiers in Pharmacology
polymyxin B
neurotoxicity
Fe3O4 nanoparticles
in vivo
susceptibility-weighted imaging
title Visualizing the Potential Impairment of Polymyxin B to Central Nervous System Through MR Susceptibility-Weighted Imaging
title_full Visualizing the Potential Impairment of Polymyxin B to Central Nervous System Through MR Susceptibility-Weighted Imaging
title_fullStr Visualizing the Potential Impairment of Polymyxin B to Central Nervous System Through MR Susceptibility-Weighted Imaging
title_full_unstemmed Visualizing the Potential Impairment of Polymyxin B to Central Nervous System Through MR Susceptibility-Weighted Imaging
title_short Visualizing the Potential Impairment of Polymyxin B to Central Nervous System Through MR Susceptibility-Weighted Imaging
title_sort visualizing the potential impairment of polymyxin b to central nervous system through mr susceptibility weighted imaging
topic polymyxin B
neurotoxicity
Fe3O4 nanoparticles
in vivo
susceptibility-weighted imaging
url https://www.frontiersin.org/articles/10.3389/fphar.2021.784864/full
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