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

Frontiers in Pharmacology

Yuanyuan Qiao¹  Saisai Yue¹  Man Xu¹  Shuang Qu¹  Qiuhong Ouyang¹  Lichong Zhu¹  Fangfei He¹  Yichun Huang¹  Runwei Li¹  Ni Zhang²  Xiaoai Wu²  Peisen Zhang³  Bin Zhao⁴  Lai Wei⁴ 

[1] College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China;Department of Psychiatry, and Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China;Department of Rehabilitation Medicine, School of Medicine, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, China;Xinxiang Key Laboratory of Forensic Toxicology, School of Forensic Medicine, Xinxiang Medical University, Xinxiang, China;

关键词: polymyxin B;    neurotoxicity;    Fe3O4 nanoparticles;    in vivo;    susceptibility-weighted imaging;   

DOI  :  10.3389/fphar.2021.784864

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown